Trigeminal neuralgiaÐpathophysiology, diagnosis and currenttreatment

T. J. Nurmikko1* and P. R. Eldridge2

1Pain Research Institute, Department of Neurological Science, University of Liverpool, Liverpool, UK.2The Walton Centre for Neurology and Neurosurgery NHS Trust, Liverpool, UK

*Corresponding author

Br J Anaesth 2001; 87: 117±32

Keywords: complications, trigeminal neuralgia; pain, neuropathic

Historical aspects

The ®rst known description of trigeminal neuralgia

(TGN), or a similar condition, was written in the

second century AD by Aretaeus of Cappadocia, a

contemporary of Galen. Also known for his descriptions

of migraine, he makes reference to a pain in which

`spasm and distortion of the countenance take place'.113

Jujani, an 11th century Arab physician, mentions

unilateral facial pain causing spasms and anxiety in

his writings. Interestingly, he suggests that the cause of

the pain is `the proximity of the artery to the nerve'.4

The ®rst full account of TGN was published in 1773

when John Fothergill presented a paper to the Medical

Society of London. He described the typical features of

the condition in detail, including paroxysms of unilateral

facial pain, evoked by eating or speaking or touch,

starting and ending abruptly, and associated with

anxiety.113 Some time earlier, Nicolaus Andre had

used the term `tic douloureux' to describe what he

thought was a new clinical entity. However, it has been

suggested, that no more than two of the patients he

described in fact had TGN.4

Sporadic observations later in the 18th and 19th

century by Pujol, Chapman and Tiffany helped to

complete the clinical picture and differentiate TGN

from common facial pain conditions such as toothache.

In the early 20th century, Oppenheim alluded to an

association between multiple sclerosis (MS) and TGN

and Patrick commented on its familial incidence.39

A wide range of treatments was in use by the beginning of

the last century. Modern neurosurgical treatment can be

traced back to 1925 when the concept of vascular

compression was introduced.29 However, it took over half

a century before microvascular decompression (MVD)

gained wide-spread acceptance as a treatment method.

Gardner and Miklos promoted the theory and modi®ed the

technique further in the 1950s and 1960s.41 It was not until

the large case series published in 1970s by Jannetta58 that a

major shift in neurosurgical practice began to appear.

Neuroablative procedures kept evolving throughout the

century, with attempts to balance the adverse effects of

neural injury with suf®cient pain control. Radiosurgery is

the latest innovation in this process.

Pharmacotherapy had little success in this condition until

Bergouignan's discovery in 1942 that phenytoin was

effective in preventing pain paroxysms.12 Soon, following

the introduction of carbamazepine for treatment of epilepsy,

controlled trials were published showing its superiority over

placebo in TGN. Since then, anticonvulsants have remained

the mainstay of pharmacological treatment, though con-

trolled trials have been surprisingly rare.

De®nition of TGN

Both the International Association for the Study of Pain

(IASP) and International Headache Society (IHS) have

suggested their own diagnostic criteria for TGN.91 143

These are remarkably similar and highlight the sudden,

explosive nature of the pain (Table 1). In further

descriptions of the condition, both classi®cations allude

to vascular compression, MS and tumours as known

aetiological causes. The IASP classi®cation makes a

distinction between TGN (including MS) and secondary

neuralgias (caused by structural lesions and injuries, but

not including MS), while IHS separates idiopathic TGN

from the `symptomatic form' depending on the presence

of a structural lesion; it is not quite clear if vascular

compression quali®es as such. Neither approach includes

reference to variant forms of TGN, which satisfy the

diagnostic criteria but display additional features as well.

British Journal of Anaesthesia 87 (1): 117±32 (2001)

Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2001

Diagnosis

Several authors have used a slightly different approach by

classifying TGN patients into subgroups depending on how

`pure' the pain is.16 20 81 99 122 140 We agree with this

viewpoint, because our own experience re¯ects the general

conclusion that the outcome is dependent on the nature of

the pain. We have also frequently witnessed, in our tertiary

referral clinic, both over- and under-diagnosing of TGN,

which seems to re¯ect dif®culties in interpreting the painful

symptoms in the context of an unnecessarily restrictive

`of®cial' de®nition.

Our own classi®cation and diagnostic criteria are pre-

sented in Table 2. We use it as guidance, rather than a ®xed

set of rules. While arbitrary, it has worked well in our hands

and greatly helped communication between various spe-

cialists. It is obvious that, in some cases, pain slowly

evolves from one category to another. A typical form of

TGN may, in prolonged cases, develop atypical signs, as

observed by Burchiel.20 By contrast, many cases of TGN

start with pain lacking the typical characteristics of TGN,

but respond well to carbamazepine, and later developing all

the hallmark signs of TGN (`pre-TGN').38

Trigeminal neuropathy, whether painful or non-painful, is

associated with a structural lesion or systemic disease.

It may be seen following direct trauma to the nerve

(e.g. supra- and infra-orbital neuralgias following facial

fractures); we also classify dysaesthesiae and anaesthesia

dolorosa following neuroablative procedures as trigeminal

neuropathy. On occasion, it can be seen caused by severe

arterial compression, usually from an ectatic basilar artery.

The pain description in this condition is different from that

in TGN and more akin to that in painful peripheral

neuropathy. Pain is usually constant and associated with

allodynia and sensory loss. Central nervous system lesions,

even if they predominantly involve the trigeminal pathways

and very occasionally mimic TGN, are not classi®ed as

either trigeminal neuropathy or TGN, but fall under the

heading of central pain.

TGN remains a clinical diagnosis dependent on a history

of sudden shooting or stabbing pain, coming as solitary

sensations or paroxysms and separated by pain-free inter-

vals. Optimally, it is the patient who volunteers this

description. However, many patients with facial pain have

considerable dif®culty in ®nding precise expressions to

convey the characteristics of their symptoms. In such a case,

the interviewer may suggest descriptive words with as little

prompting as possible. Some patients identify the type of

pain if an acoustic equivalent of the pain is provided, for

example, by the interviewer sharply clapping his hands.

Although the McGill Pain Questionnaire has been shown to

be useful in differentiating a group of TGN patients from

those with other facial pains,90 our observations suggest

that, in individuals, taking a careful history is unsurpassed in

providing the most reliable elements for the diagnosis.

Patients with atypical TGN also give the history of

stabbing or shooting pains. Unlike in typical TGN, they

relate a history of other kinds of pain as well. Many have

constant or near constant discomfort on the same side of the

face. We are not aware of studies focussing on atypical

forms. Many patients we see are those with recurrent TGN

with a history of previous neuroablative procedures. It

remains a possibility that compression of the nerve, when

protracted, can lead to intrinsic changes in the nerve and

modify the clinical picture.20

In addition, non-verbal behaviour may be very helpful in

aiding the diagnosis. Patients with severe TGN either wince

or interrupt their speech as a result of a tic. Many show

major aversion to anyone or anything touching the face.

This may, in fact, in¯uence the clinical examination. By

contrast, patients with other types of facial pain, including

trigeminal neuropathy, usually seem not to be bothered by

the their hand or the examiner's hand touching their face.

Differential diagnosis

The list of differential diagnoses is long and includes a

number of pathological conditions affecting the sinuses,

teeth, temporomandibular joints, eyes, nose, and the neck.

Most of these are easily ruled out after the interview and

brief clinical examination. However, a few conditions

remain that bear considerable similarity to TGN and are

listed in Table 3.

Other cranial neuralgias (glossopharyngeal neuralgia,

neuralgia of nervus intermedius, neuralgia of the superior

laryngeal nerve, and occipital neuralgia) can all cause

diagnostic dif®culty. These neuralgias are rare and can

produce pain that is identical to that of TGN. However, the

location is different.

Aetiology of TGN

There are obvious problems in determining aetiological

causes for a syndrome, which is formulated on the basis of

Table 1 De®nition of TGN provided by the International Association for the Study of Pain, IASP91 and International Headache Society, IHS143

IASP de®nition IHS de®nition

Sudden, usually unilateral, severe brief stabbing recurrent

pains in the distribution of one or more branches of the

Vth cranial nerve

Painful unilateral af¯iction of the face, characterized by brief electric shock like pain

limited to the distribution of one or more divisions of the trigeminal nerve.

Pain is commonly evoked by trivial stimuli including washing, shaving, smoking, talking,

and brushing the teeth, but may also occur spontaneously. The pain is abrupt in onset and

termination and may remit for varying periods

Nurmikko and Eldridge

118

subjective pain rather than hard signs or laboratory abnor-

malities. However, in the last three decades, evidence has

been mounting that in a large proportion of cases,

compression of the trigeminal nerve root at or near the

dorsal root entry zone by a blood vessel is a major causative

or contributing factor. There are several lines of evidence

that support this view. First, novel imaging methods (MRI)

and observations during posterior fossa surgery for TGN

have consistently shown a blood vessel in contact with the

nerve root.13 88 Second, elimination of the compression

leads to long-term pain relief in most patients.10 Third,

intra-operative recordings show immediate improvement in

nerve conduction following decompression, ®tting with the

general experience that patients tend to wake up from the

operation pain-free.76 Fourth, sensory functions recover as

well following decompression (though this recovery is

slower than that in nerve conduction).92

Some authors have questioned the signi®cance of the

vascular compression by pointing out that it is not unusual to

see blood vessels in the vicinity of or touching the nerve

during a routine autopsy in patients with no history of

TGN.2 3 However, as underlined by many others, the critical

abnormality is vascular contact at the dorsal root entry zone,

rather than more distally; such is seen in 3±12% of

trigeminal nerves at autopsy.48 50 The way the autopsy is

carried out may be relevant. Hamlyn and colleagues have

suggested that their method of positioning the cadaver to

mimic the positioning during the actual operation and

perfusing the arteries and veins at physiological pressures to

prevent them from collapsing leads to a more reliable

assessment of any signi®cant neurovascular compression.48

They found a blood vessel contact in 13% of the cadavers,

but without concomitant grooving of any of the affected

nerves. A contact at the level of the dorsal root entry zone by

an artery was found in 3% and by a vein by 6% of their

material.48

Of other known aetiological factors, the association of

MS with TGN is well established.60 108 115 MS is seen in

2±4% of patients with TGN.51 60 61 115 Conversely, TGN is

diagnosed in 1±5% of patients with MS.27 53 94 115 123 In a

small proportion of patients with MS, TGN is the ®rst

manifestation of the disease. These patients are younger

than the TGN population as a whole and their neuralgia is

more frequently bilateral. A latent demyelinating disease

Table 2 Comparison of de®nitions of TGN. *Key items

TGN (IASP andIHS de®nition)

Typical TGN(Liverpool criteria)

Atypical TGN(Liverpool criteria)

Trigeminalneuropathy(Liverpool criteria)

Site* Unilateral Unilateral Unilateral Uni- or bilateral

Quality of pain* Sharp, stabbing,

burning, super®cial

Sharp, shooting,

stabbing, lingering

aftersensations

Sharp shooting,

stabbing, lingering

aftersensations,

burning, smarting

Dull or sharp,

smarting, steady

pain with shooting

sensations superimposed

Duration of pain* Brief A few seconds at most Several seconds Any duration,

usually hours

Duration ofparoxysms

Seconds to

2 minutes

Seconds to minutes Seconds to minutes Continuous with

pain-free spells

Refractoryperiod

Yes Yes Yes No

Continous pain No No Yes, not severe Dominant feature

Allodynia* Limited trigger zones Small trigger zones Small trigger zones Large allodynic areas

Associatedfeatures

Slight ¯ush Vasodilatation,

swelling seen with

severe pain

Vasodilatation,

swelling seen with

severe pain

Variable

vasodilatation and

swelling, may be

constantly present

Radiation None outside

affected division

None outside

affected division

None outside

affected division

May extend outside

trigeminal territory

Provokingfactors*

Eating, talking,

washing face,

brushing teeth, smoking

Touching, speaking,

eating, drinking, cold,

not heat, movement

Touching, speaking,

eating,

drinking, cold,

occasionally

heat, movement

Same as atypical TGN

Variability ofpain

Stereotyped Some variation De®nite variation De®nite variation

Sensory loss* None Not detectable with

bedside tests QST

may be abnormal

May be detectable

with bedside tests

QST usually

abnormal

Prominent, easily

detected with

bedside tests,

con®rmed by QST

Pain behaviour Not discussed Aversion to touch

guarded speech

Aversion to touch

guarded speech

Tolerates touching

speech not affected

Course of pain* Spontaneous

remissions

Early remissions

pre-TGN

Early remissions

previously typical

TGN

No remission; slow

progression

TGN±pathophysiology, diagnosis and current treatment

119

should be considered in young patients with TGN and

appropriate diagnostic tests performed, as disease-modify-

ing treatment for MS is emerging.57

Neuropathological and imaging studies suggest that the

common denominator in patients with typical TGN and MS

is the involvement of the trigeminal nerve entry zone in the

pons.42 60 In contrast, plaques in other parts of the brain

stem or elsewhere in the CNS do not necessarily lead to

development of TGN. Interestingly, there are reports of

vascular compression of the trigeminal nerve in patients

with MS,16 17 89 and pain relief following decompression,

though the results are less favourable than in other TGN

subgroups.16 17

Tumours, usually posterior fossa meningiomas or neuro-

mas, are found in 2% of patients who present with typical

TGN.26 The localization of the tumour dictates the nature of

facial symptoms. Tumours affecting the peripheral branches

or the Gasserian ganglion usually give rise to sensory

change and constant pain, in other words, trigeminal

neuropathy.19 26 Slowly growing tumours which distend

the trigeminal root rather than invade it, are usually found in

TGN.26 In Cheng's series, the average delay in diagnosis of

the tumour was 6.3 yr. Half of the patients developed

sensory or motor de®cits later.

Pathophysiology

Although there is general agreement that none of the many

existing theories fully explain all known characteristics of

TGN pain67 129 the bulk of current evidence points to the

trigeminal nerve rather than the CNS as the site of

generation of TGN pain.105 More speci®cally, the existing

evidence suggests that a slowly evolving process, whether a

compression exerted on the nerve by a blood vessel or

tumour or alteration of neural functions by an MS plaque at

the level of the dorsal root entry zone, leads to increased

excitability in some of the trigeminal afferents and subse-

quently to typical TGN.

Part of the controversy that surrounds the pathophysiol-

ogy of TGN is based on misquotations and inaccuracies.

Against popular belief, sensory impairment in TGNÐalbeit

smallÐhas been documented by several groups, both using

quantitative sensory testing and neurophysiological meth-

ods.18 75 100 As already mentioned, these changes normalize

following successful MVD.76 92 The trigeminal ganglion in

TGN is not normal but shows unique pathological changes,

such as degenerative hypermyelination and formation of

microneuromata, not explained by tissue artefacts, effects of

aging or occult disease.11 62 63 The ganglion cells

themselves appear mostly intact. While the exact mechan-

isms of how these changes have come about is not clear, it is

of interest that such changes were reported in a patient with

MS and TGN.11 At the site of vascular compression of the

trigeminal root, electron microscopic studies show demye-

lination and remyelination.63 106

It has been suggested25 that lack of neurogenic in¯am-

mation in TGN is evidence against a major peripheral

nervous system involvement. However, vasodilatation is

known to occur in TGN and it normalizes when pain is

controlled.101

A puzzling fact in TGN is that very different

treatments yield seemingly similar results in controlling

TGN pain. However, closer inspection of the long-term

effects suggests that simple blocks or minimally destruc-

tive peripheral procedures lead to transient pain relief,

much shorter than seen in more proximal lesions or

decompression.10 44 95 126 138 Also, following neuroa-

blative procedures, the degree of sensory loss correlates

positively with the duration of pain relief.126 If one

assumes that the dynamic pain of TGN re¯ects a state

of hyperexcitability in the trigeminal afferents rather

than a ®xed anatomical aberration constantly driving the

pain mediating ®bres, then either permanent destruction

of the relevant ®bres or complete restoration of their

normal functions (e.g. following decompression) will

Table 3 Differential diagnosis of TGN. *SUNCT, Short-lasting, unilateral, neuralgiform headcahe with conjunctival injection and tearing; **CPH, chronic

paroxysmal hemicrania. Sources: Goadsby and Lipton,43 Merskey and Bogduk,91 and Zakrzewska141

Condition Location ofpain

Duration ofpain or attack

Shooting painor paroxysms

Autonomicsymptoms

Pain relief withcarbamazepine

Comments

Cluster headache Retrobulbar,

cheek, chin

20 min to

hours

Only superimposed

on deep dull pain

Prominent Slight Triptans help

Alcohol provokes

SUNCT* Forehead,

retrobulbar

5 s to several

minutes

Yes Prominent None Almost exclusively in

women; rare

CPH** Forehead,

retrobulbar

2±45 min No Prominent None Responsive to

indomethacin

Cracked tooth

syndrome

Upper jaw

lower jaw

Seconds Yes None None Provoked on biting

and chewing

Jabs and jolts

syndrome

Anywhere in

the head

Seconds Yes None Good No precipitating factors

Post-herpetic neuralgia Forehead, eye,

cheek (rarely)

Continuous Superimposed

background pain

Variable, mild Variable, usually

modes

History of shingles

Tactile allodynia,

Sensory impairment

Giant cell arteritis Forehead, neck,

temple

Continuous None None None Jaw claudication

Nurmikko and Eldridge

120

only achieve sustained pain relief. The key feature of

TGN pain is its very dynamic nature, which is dif®cult

to explain in purely anatomical terms.105

It is hard to dismiss as insigni®cant the observations

made by numerous neurosurgeons during decompressive

surgery that arterial compression of the root at the

dorsal root entry zone is the common ®nding in typical

TGN.10 20 68 73 78 79 104 111 120 Similarly, in MS

patients suffering from TGN, a common ®nding is the

plaque extending into the dorsal root entry zone.42 The

dorsal root entry zone represents the junction between

the peripheral and central myelins of Schwann cells and

astrocytes. The central branches of the unipolar ganglion

cells enter the pons through this transition zone on their

course toward the brainstem and spinal nuclei. Any

process at this level can potentially alter the function of

the whole neurone.

The fact that TGN pain is not continuous but

paroxysmal speaks against a simple compression induced

generation of ectopic impulses at the level of the injury.

It is more likely that the paroxysms of pain in this

condition represent spontaneous discharges in select

neurones whose threshold for repetitive ®ring has been

altered. To comply with the characteristics of TGN,

such ®ring should not only occur spontaneously but be

produced frequently by innocuous tactile stimuli. Recent

observations have shown that dorsal root ganglion cells

possess properties that, in certain circumstances, lead to

this type of ®ring behaviour.6 Following spinal nerve

injury, in which afferent neurones are axotomized close

to their soma, most of the ectopic barrages originate in

the dorsal root ganglion.83 Intracellular recordings have

indicated that this is because of an increase in

subthreshold oscillations in the resting membrane

potentials of a subpopulation of A-neurones reaching

threshold.83 Increased spike activity can in turn depolar-

ize and cross-excite hyperexcitable neighbouring C-

cells.5 If suf®cient neurones are recruited into this

spreading cluster of discharging cells, it will lead to a

nociceptive signal perceived as pain.5 6 105 That such a

signal would abruptly stop, as happens in TGN, is

because of the inherent cellular self-quenching mechan-

isms.

As suggested by Rappaport and Devor,105 the above

cross-excitation may be at the root of the unique pain seen in

TGN and offers a logical explanation for the extraordinary

initial responsiveness of pain in TGN to almost any

procedure aimed at the nerve. We think it is unlikely that

the generator of pain is located in the central nervous system

but central sensitization may well develop following

prolonged barrage of nerve impulses which can explain

the development of some features of atypical TGN. Equally,

continuous pain in the atypical form can result from the

progressive damage to the central terminals of trigeminal

afferents, which become the source of continuous ectopic

discharges.20

Investigations

No speci®c tests exist for the diagnosis of TGN. There is no

excuse for not carrying out a clinical examination, including

assessment of cranial nerve function, given the frequency of

MS and tumours found in this population. De®nite facial

sensory loss or other cranial nerve dysfunction, if it cannot

be explained by a previously known injury to the nerve,

should prompt cerebral imaging.

Even in typical TGN, imaging studies may well be of

use. Following the ®rst reports of successful use of MRI

in detecting vascular compression of the nerve in TGN.8

127 Meaney and colleagues developed a speci®c tech-

nique to optimally image the relationship of the nerve

and the blood vessels in its vicinity (magnetic resonance

tomographic angiography, MRTA).89 Essentially, by

choosing speci®c scanning parameters to visualize

blood vessels as high signal intensity structures and

using thin slices, they were able to perform reconstruc-

tions around the nerve in any orientation. While arteries

were easily identi®able, veins could be properly

visualized only after enhancement with i.v. gadolinium

(Figs 1 and 2). They validated this method in 50

patients with 55 symptomatic nerves (®ve patients had

bilateral TGN) who underwent posterior fossa explor-

ation. In all, 52 explorations were carried out.

Neurovascular contact was con®rmed at operation in

all 49 cases suggested by MRTA. A further case with

negative MRTA had no vascular contact. There were

two false negative MRTAs and no false positives. This

corresponds to a sensitivity of 100% and speci®city of

96%.89

In a similar study of 27 patients with unilateral TGN,

neurovascular compression, or its absence as shown by

MRTA, was con®rmed in 24 cases.13 There were two false

positives and one false negative (sensitivity of 92%,

speci®city of 50%). A further small study, in which

visualization of nerve dislocation or actual compression

only were accepted as positive ®ndings, led to 100%

speci®city at the cost of low sensitivity (44%).85

Because to date there are no prospective studies compar-

ing different facial pain groups and healthy controls,

evaluated by radiologists blinded to the condition and

side, the accuracy of MRTA in differentiating TGN form

other painful trigeminal neuropathies remains uncertain.

Therefore, MRTA cannot be used to diagnose TGN. Our

current practice is to use MRTA to help in determining the

likelihood that, at operation, a signi®cant vessel contact will

be found.

Several groups have developed electrophysiological

techniques for assessment of trigeminal nerve function in

the clinic.28 56 75 There is insuf®cient evidence of their

usefulness in either con®rming or ruling out TGN.

However, abnormalities in tests for eye blink and jaw

re¯exes strongly point to trigeminal neuropathic pain or

`atypical facial pain'.56

TGN±pathophysiology, diagnosis and current treatment

121

Treatment

Procedures

MVD

Since the original theory, outlined by Dandy in 1925, of

vascular compression as a prominent feature of TGN, it took

almost half a century until MVD was accepted as one of the

major surgical methods for treating this condition.

Advances in neuroanaesthesia, adoption of the operation

microscope and developments in surgical techniques during

this time helped to make the procedure safer and more

effective.

In MVD, the target area lies at the nerve±pons junction.

The posterior fossa is approached through a suboccipital

craniotomy. After aspiration of the cerebrospinal ¯uid, the

operator advances toward the nerve by gently retracting the

superolateral margin of the cerebellum. The most common

®nding is a segment of the superior cerebellar artery

compressing the nerve at the root entry zone111 (Fig. 3).

Less frequently, the anterior inferior cerebellar artery or the

superior petrosal veins are the cause of the compression.111

After the arachnoid is dissected and the vessel freed, the

operator places a piece of shredded Te¯on felt between the

vessel and the nerve to separate them.

Monitoring of brainstem-evoked potentials during the

operation (to prevent post-operative hearing loss) frequently

shows temporary changes, because of traction on the eighth

cranial nerve. These usually disappear if the retractor is

temporarily relaxed. Most authors recommend partial

section of the root if no vascular compression is found or

the artery cannot be mobilized. Adams has recommended

deliberate bruising of the nerve in addition to decompres-

sion,3 but we have not found any evidence that such a

manoeuvre improves the outcome.

There is no age limit for the procedure as long as the

patient is ®t for general anaesthesia. In our recent

retrospective study in patients over 70 yr of age, pain relief

and complications were no different from those seen in a

group of patients under the age of 50.59 There are anecdotal

reports of MVD carried out in children less than 18110 114

with similar results. Interestingly, venous compression

appears much more common in this age group than in

adults.

Several published series suggest a high level of initial

success with MVD, most patients (87±98%) experiencing

Fig 1 MRTA of a patient with right TGN. Coronal reconstruction at the

level of mid-pons showing the right trigeminal nerve (thin arrow) being

compressed by an artery (thick arrow).

Fig 2 MRTA, sagittal reconstruction, showing the trigeminal nerve (star) and the artery compressing it from above (arrow). Same patient as in

Figure 1.

Nurmikko and Eldridge

122

immediate pain relief.10 21 68 73 78 104 120 Those series that

present the proportion of patients with unrelieved or

recurrent pain using KaplanÐMeier plots, show relatively

similar results.10 21 104 At 1±2 yr the incidence of complete

pain relief is 75±80%. After 8±10 yr, this proportion has

been reduced to 58±64%, with a further 4±12% suffering

from minor recurrence only.

Overall, results from de®nite arterial compression are

better than when only an offending vein is found.10 68 104 In

a recent retrospective survey, the authors observed a

recurrence rate of 31% in patients with TGN caused by

venous compression. In most cases, the recurrence took

place within the ®rst 12 months of the operation.79 Reports

of worse outcome after MVD in those patients with a history

of previous neuroablative surgery are not substantiated by

other studies.9 10 21 54 Opinions differ as to what is the best

policy in cases of recurrence following MVD and both

re-exploration and neuroablative procedures have been

recommended.74 80 109 Findings at re-operation are so

varied that it is unlikely that any consensus will be arrived

at. Perhaps with the advent of imaging, it will be possible to

pinpoint the cause of recurrence and decide on the most

appropriate course of action.

In experienced hands, MVD is well tolerated. Although in

early series a mortality rate of 0.2±1% was described,

surgical innovations have since improved the results. In two

large recent series consisting of 44473 and 199586 patients,

no deaths were reported. Cerebellar injury was reported in

0.45%, eighth nerve injury in 0.8% and CSF leak in 1.85%

in a recent retrospective study.86 However, other centres

report higher complication rates.68 104 It is likely that the

results are much better in centres that operate frequently on

these patients and have regularly reviewed their technique

and improved perioperative monitoring systems.

Although the popularity of MVD has undoubtedly

increased in the last two decades, there is ongoing debate

regarding its advantages over neurodestructive proced-

ures.67 126 In the absence of prospective, randomized

comparative studies on this issue, the way various surgical

treatments are used depends on clinical judgement which

inevitable varies across centres.

Radiofrequency gangliolysis

Disillusionment with complications resulting from an

uncontrollable spread of alcohol or phenol injected into

Meckel's cave for treatment of neuralgia led to the

development of thermocoagulation of the Gasserian gan-

glion in the 1930s. The concept was ®rst explored by

Kirchner whose large series was published in 1942.66 The

technique was modi®ed to produce more precise and safer

lesions by several authors. In 1974, Sweet presented his

method which, by and large, is used today.124 Essentially, it

involves a selective partial lesioning of the affected

ganglion or retrogasserian root. Sweet and Wepsic sug-

gested that what resulted from thermocoagulation was

selective loss of pain mediating thinly myelinated or non-

myelinated ®bres.124 This hypothesis has been challenged

by observations that, following this procedure, all sensory

functions are found to be affected.47

The procedure is carried out in the intermittently

anaesthetized patient under ¯uoroscopic control. The

radiofrequency needle is inserted through the foramen

ovale into Meckel's cave using bony landmarks. The

relationship of the trigeminal rootlets to the foramen ovale

is such that by stepwise advancement of the needle the third,

second and ®rst divisions will be in succession stimulated,

the closer to the clival line the needle tip is (Fig. 4). As soon

as the needle has entered Meckel's cave, aspiration will

usually yield CSF. Once the needle has travelled the pre-

planned distance, the patient is allowed to awake, the stylet

replaced by the electrode and stimulation of the nerve root

carried out. The paraesthesiae elicited must conform to the

location of the neuralgia, otherwise the needle must be

repositioned. Once appropriate siting has taken place, the

patient is anaesthetized again for thermal lesioning. This is

performed in cycles of 45 to 90 s at temperatures of

60±90°C. After each lesioning the patient is awakened and

manual sensory testing of the face carried out. Additional

thermal lesions are performed until clear hypalgesia has

ensued.

Use of ¯uoroscopy, and stepwise increases of needle

temperatures make this procedure a relatively safe alterna-

tive. Most patients only need an overnight stay. Mortality is

virtually nil and severe complications (cerebral haemor-

rhage, carotid-cavernous ®stula, meningitis, and cranial

nerve lesions) are very rare.

Unfortunately, this method can cause dysaesthesiae in up

to 25%, mostly mild. Dysaesthesiae requiring medical

treatment are seen in approximately 8%. Unfortunately, the

quality of life in these patients is not improved even if the

Fig 3 Microscopic view of the trigeminal nerve (star) showing an arterial

loop (triangle) compressing it. A vein (cross) is seen in close proximity

to the nerve as well.

TGN±pathophysiology, diagnosis and current treatment

123

original pain has been controlled. There is some indication

that this adverse effect is more common in patients with

atypical TGN. Frank anaesthesia dolorosa is rare (mostly

under 1%). Corneal anaesthesia is a potentially serious

complication as it may lead to keratitis in 1±2% of cases.

Other rare complications include meningitis, carotid-

cavernous ®stula, intracranial haemorrhage, and cranial

nerve de®cits.

The success of pain relief re¯ects patient selection and the

degree of sensory loss the operator is keen to achieve.

Zakrzewska identi®ed 38 reports of RFL from the literature,

with variable follow-up.142 The variability in patient

selection and follow-up make comparisons very dif®cult.

We have found three published prospective studies on the

long-term ef®cacy of RFL. Taha and colleagues reported

results from a prospective follow-up of 100 patients (from

the original group of 154 patients).126 Those with mild

hypalgesia had a recurrence rate of 60% at 3 yr, after which

no more recurrencies occurred. Those with deep hypalgesia

or actual anaesthesia had a recurrence rate of 20% at 15 yr.

No lifetime analysis was provided. Zakrzewska and col-

leagues reported on 31 patients with pure TGN and 17 with

atypical (or `mixed') TGN in a prospective longitudinal

study.140 In this series, `pure' TGN patients seem to have the

characteristics of the `typical neuralgia' category whereas

`mixed' neuralgia cases were similar to our `atypical TGN'

category; sensory abnormalities were not mentioned but

depression was common in this group.140 The lifetime

analysis indicated a steady increase in the proportion of

patients with recurrent pain in both groups. At 3 yr, 40% of

both groups complained of recurrent TGN. However,

patients belonging to the `mixed' group reported other

facial pain in 75% of cases (while the same was true of 12%

of patients with typical TGN).

In a study of 215 patients, the vast majority experienced

immediate pain relief (92%).118 Recurrence of TGN pain

occurred in 27% at a mean follow-up of 32 months. The

authors did not state the number of patients lost to follow-

up. Side effects were similar in intensity and quality to those

reported in other series.

Certain conclusions can be drawn from these prospective

and retrospective series. Immediate pain relief in typical

TGN is high, with diminution of effectiveness over time so

that at 3 yr one-third of patients will have recurrent

neuralgia. Long-term annoying paraesthesiae following the

procedure is experienced by 5±10%, but frank anaesthesia

dolorosa is rare. Life-threatening complications occur in

less than 1%.

Glycerol gangliolysis

The method was introduced by HaÊkansson after a fortuitous

discovery, during the development of a stereotactic tech-

nique for gamma radiation, that glycerol mixed with

tantalum powder not only visualized the trigeminal cistern

but also abolished pain in patients with trigeminal neuralgia.

The ®rst series consisted of 75 patients with a mean follow-

up of 18 months.46 The method was quickly adopted by

several centres so that by 1993 over 20 case series had been

published describing results in some 2500 patients.141 The

results were rather variable and, in some cases, early

enthusiasm was followed by quick disappointment. Several

authors have given up the method, either because of poor

long-term results or adverse effects125 135 while advocates

of the procedure point out that, with a proper technique, not

only is the procedure well tolerated but yields good long-

term results .47

The procedure can be done under local anaesthesia in

fully awake patients, although mild sedation is usually used.

The needle is inserted into the trigeminal cistern through the

foramen ovale using similar trajectories as in radio-

frequency lesioning and balloon compression. Needle

positioning must be precise to ensure the tip lies in the

ganglion and not the subarachnoid space beneath the

temporal lobe.135 Free CSF ¯ow is the norm, except in

previously treated cases. Fluoroscopic control is mandatory

but the use of radio opaque contrast (cisternography) to

visualize the cistern varies from centre-to-centre.

(HaÊkansson strongly advises its use47). Once the needle is

optimally placed, the patient is brought into a sitting

position and a small test dose of sterile anhydrous glycerol

injected. This is followed by small dose increments up to a

total of 0.1±0.4 ml, depending on the divisions involved.

Some authors argue that the patient's head must be

positioned in a speci®c way to allow the glycerol to reach

the intended root. Patients are usually able to perceive the

effect of the injection as a tingling or burning sensation in

Fig 4 Lateral radiograph of radiofrequency needle inserted into the

gasserian ganglion.

Nurmikko and Eldridge

124

the affected divisions. They remain in the sitting position for

2 h after the injections.

Alhough pain relief is usually immediate, it may take up

to 7 days to occur in some patients.7 135 Most authors report

initial pain relief in over 80% of their patients but long term

results are highly variable. At 12 months, reported recur-

rence rates vary from 10 to 53%. At 5 yr, 34±83% of the

patients will have experienced recurrence of neuralgia.36 40

46 117 122 135 The authors differ in their views on the

usefulness of repeat lesioning in case of recurrence. Patients

with atypical TGN or painful trigeminal neuropathy are

likely to have less favourable results.36 99 119

This method is generally well tolerated and mortality is

negligible. There are anecdotal reports of meningitis, cranial

nerve palsies, and local haematomas. Activation of herpes

labialis occurs in one third and permanent masseter

weakness is seen in a small proportion of patients.7 99 132

Although sensory change is usually thought to be limited

and not necessary for pain relief,31 32 Steiger showed that in

a series of 122 patients treated with glycerol rhizolysis, post-

operative sensory loss was directly correlated with a good

long-term outcome.122 Reports of dysaesthesiae vary from 0

to 44%. This variability may, in part, be a result of many

authors including in their series patients previously treated

with neuroablative procedures.99 117 132 Keratitis related to

corneal sensory loss is reported in most series although it is

very rare.

Glycerol rhizolysis has probably caused more contro-

versy than any other procedure with strong views expressed

by both proponents and critics.36 40 47 125 135 It seems that in

centres where this method is commonly used, and the

technique meticulously employed, the results are similar to

those with other ganglion-level procedures.

Balloon compression

In the 1950s, several groups reported that compression of

the ganglion seemed to produce similar, if not better, results

compared with the techniques used at the time for root

decompression. In 1983, Mullan and Lichtor published their

®rst series of 50 patients who had undergone compression of

the trigeminal ganglion using a Fogarty-type balloon.95 This

procedure is performed under general anaesthesia. Using

¯uoroscopic control, a guide needle is inserted into the

foramen ovale, but not beyond it. Through the needle, the

Fogarty catheter is advanced until its tip lies in Meckel's

cave and the balloon is slowly in¯ated with 0.5±1.0 ml of

contrast dye until it occupies the cave, ensuring adequate

compression (Fig. 5). Total compression times vary from

1±6 min.1 95 This produces only a mild sensory loss with

immediate pain relief in practically all patients.

Interestingly, masseter weakness is very common although,

in most cases, there is complete recovery in a matter of

weeks.95 The patient usually only requires an overnight

stay.

This method has been used in both typical and atypical

TGN, in patients with MS and in those who have had

previous neurodestructive procedures (or MVD) for their

TGN.36 95 Recurrence is reported in 6±14% in the ®rst year.

Very few studies employing long-term follow-up are

available. In Abdennebi's series, one-third needed re-

operation during a mean follow-up of 4.3 yr.1 Lichtor and

Mullan obtained slightly better results in that recurrence was

seen in 20% of patients at 5 yr follow-up, and 28% of a small

number of patients followed even longer (up to 10 yr).81

Troublesome dysaesthesiae following the procedure are

reported in all series. Mullan and Lichter comment on 6% of

their patients having signi®cant discomfort from these

dysaesthesiae and Fraioli and colleagues indicate that 7%

required transient medical treatment for the same prob-

lem.36 95 In Abdennebi's series, severe dysaesthesiae were

seen in 1.5% and `moderate' dysaesthesiae in a further

15%.1 Interestingly, 11% of patients were reported to be

discontent or very discontent with the outcome. Many had

atypical TGN with dysaesthesia possibly as a result of

previous surgery and this dysaesthesia was not relieved by

balloon compression.81

Stereotactic radiosurgery

Well-localized lesions in the trigeminal nerve can be

generated also by stereotactic radiosurgery. Some 50 yr

ago, Lars Leksell developed a radiosurgical tool, the so-

called `Gamma Knife', to treat functional brain disorders as

an alternative to open intracranial procedures. Among the

®rst patients he treated were two with TGN. However, it

took decades before the technique had been re®ned and

imaging developed suf®ciently to allow precision targeting

for the procedure.69 Initial attempts at irradiation of the

Gasserian ganglion yielded discouraging results. However,

in recent years, the target has been the proximal trigeminal

root near the pons, with a much improved outcome.69

The Gamma Knife is a focused array of 201 intercepting

beams of gamma radiation, produced by separate cobalt

sources. A stereotactic frame is ®rst secured to the patient's

head, followed by MRI to identify the trigeminal nerve.

Radiosurgery is carried out with the patient supine with the

head under the collimator helmet. Local anaesthesia is used

for securing the frame and irradiation is frequently carried

out under mild oral or i.v. sedation.69 70 71

The dose used is 70±90 Gy. Pain relief is usually not

immediate. The mean time to pain relief in two series was

approximately one month.70 134 The histopathological

effects of radiosurgery on the trigeminal root were inves-

tigated in an experiment performed on two male baboons.72

Six months after radiosurgery at 80 and 100 Gy, focal

axonal degeneration and necrosis were observed. This

appears to correlate with contrast enhancement seen on MRI

months after radiosurgery. No changes in the ganglion were

seen.72

In 1996, the ®rst systematic study on the use of

stereotactic radiosurgery in TGN was published.70

Although a multicentre study involving 50 patients, it was

designed to evaluate various techniques and radiation doses.

TGN±pathophysiology, diagnosis and current treatment

125

Nevertheless, at a median follow-up of 18 months, 58%

were pain-free, 36% had signi®cant pain relief, while 6% of

procedures were considered to have failed. In two more

recent single-centre studies, more favourable results were

obtained. Young and colleagues treated 51 patients with

TGN with a maximum dose of 70 Gy with excellent

immediate effects in 74% and good (pain reduction of more

than 50% with or without medication) in 14%.134 At a mean

follow-up of `more than a year' the incidence of excellent,

good and failed relief were 70, 10, and 20%, respectively.134

In a study involving 106 patients with radiosurgery doses

ranging from 70 to 90 Gy, the long-term (median 18 months,

range 6±48 months) results were excellent (no pain) 60%,

good (50±90% pain reduction) 17%, and poor (less than

50% pain reduction) 24%.71 In this latter group, only 22

patients had not had previous surgery. The majority had

undergone either radiofrequency or glycerol gangliolysis

while one-third had undergone MVD. In both studies, side

effects were minimal. Facial paraesthesiae were reported in

10%.71

This method seems a valuable addition to the existing

treatments as it is very patient-friendly and safe. However,

as yet, long-term results are lacking and it is not clear which

of the other methods can be applied in case of recurrence.

Currently, the limiting factor for this treatment is the small

number of centres capable of providing this service.

Peripheral neurectomy

Neurectomies of the affected branches were attempted for

the ®rst time in the 18th century with variable success.

Mainly employed by present day maxillofacial surgeons, the

technique is too under-reported to allow evaluation of its

usefulness against other treatments. Khanna and Galinde64

described a successful outcome at 1±5 yr follow-up in 75%

of 118 patients who underwent several neurectomies while

Mason84 achieved a success rate of 64% at 12 months and

26% at 4 yr. In a subgroup of 11 patients who had infra-

orbital neurectomy followed by occlusion of the canal,

seven were pain-free at 4 yr. However, he makes a point

that, in this retrospective analysis, careful selection of

patients was employed conforming to the strictest of TGN

criteria. Recently, a small retrospective series was published

on 40 patients with typical TGN who underwent this

procedure. The majority had previously undergone radio-

frequency lesions.96 At a follow-up of 24 months, six (15%)

had experienced a recurrence; these were treated success-

fully with repeat neurectomies. Surprisingly, none of the

above authors discuss adverse effects at all.

By contrast, Danish investigators found that, during a

mean follow-up of 7 yr, 78% of patients who had undergone

neurectomy experienced a recurrence. One-half of the

patients had their ®rst recurrence within a month. In their

series, neurectomy (as well as alcohol block) compared

unfavourably with radiofrequency lesioning.102 Compli-

cations (mainly eye problems and dysaesthesiae) were

reported in just under 10%, similar to those who had

undergone radiofrequency lesioning or alcohol blocks.

Neurectomies are performed through an incision made at

the eyebrow (supra-orbital nerve) or intraorally (infra-

orbital, alveolar and lingual nerves). All branches are

divided and avulsed under magni®cation. The relevant

foramen is blocked by bone wax, wooden sticks or silicone

plugs. The remnant of the nerve may also be cauterized.

Despite these efforts, remnants may be found on re

exploration and dealing with them in the same way is said

to lead to pain relief.96

From the existing scarce literature, it cannot be concluded

how this procedure sits on the map of TGN management. It

does not appear to offer any bene®t over other well

established surgical procedures, but it may be useful in cases

where other treatments have failed and the patient or doctor

are reluctant to consider procedures aimed at the ganglion or

root.

Cryotherapy

Cryotherapy is a surgical technique in which a peripheral

branch of the three major divisions of the trigeminal nerve is

exposed and frozen by direct application of a cryoprobe

with a tip temperature from ±50 to ±70°C.97 The patient

requires i.v. sedation or general anaesthesia. Although well

tolerated by patients, the results are modest. Of 145 patients

who underwent 1±11 sessions of cryotherapy (56% had

more than one session), the effect lasted less than 6 months

in one half and at 12 months, only 27% were pain-free.138

Perhaps because of the peripheral approach, the pain broke

through in another nerve, requiring a repeat procedure.

Almost two-thirds had to remain on their previous medica-

Fig 5 Balloon compression in TGN. Lateral radiograph showing the

distended balloon in Meckel's cave. Courtesy of Mr Varma, The Walton

Centre for Neurology and Neurosurgery NHS Trust.

Nurmikko and Eldridge

126

tion. Although improvement in individual nerves was better,

from the pain point of view, cryosurgery falls short of

results obtained either with procedures aimed at the

ganglion or the root.

Some 4% of patients develop post-operative local infec-

tion requiring treatment with antibiotics. Frank dyaesthesiae

are not common but a sizable proportion of patients, (40%)

describe a facial pain whichÐaccording to the authorsÐ

`does not have the characteristics of TGN or anaesthesia

dolorosa'.138 As in the case of neurectomy, we ®nd little

reason to advocate the use of this method except in

circumstances where more sophisticated surgical or radi-

ation treatments cannot be carried out.

Alcohol block

Peripheral and ganglionic alcohol blocks have been used

since the beginning of the last century but have fallen into

disrepute within the neurosurgical and neurological com-

munity, mainly because of capricious results and reports of

adverse effects.103 141 Those still employing the technique

underline its simplicity and the fact that results are similar to

other peripheral ablative procedures. Unfortunately, there is

little documentation on the sensory aftermaths of this

procedure. In a retrospective analysis of 45 patients treated

with one or several alcohol blocks, 84% of patients had a

recurrence of pain during the mean follow-up of 8 yr.102

One-half had a recurrence within a month. As an aftermath,

eye problems and dysaesthesiae were reported by 5±8%.102

In a report of 413 alcohol blocks performed on 82 patients

over a period of 22 yr, `serious' complications were reported

in three patients only (cutaneous necrosis, development of

bony sequestrium, diplopia).33 Other complications include

facial nerve palsy and loss of vision.141

Alcohol injections must be administered directly into the

nerve and they are painful and cause local oedema. In our

view, the high risk of recurrence of pain combined with a

moderate risk of dysaesthetic and other complications

exclude this procedure from routine use, except in frail or

medically un®t patients, or those who refuse more extensive

surgery.

Other peripherally targeted procedures

Other methods of producing controlled peripheral neural

trauma include radiofrequency lesions and injections using

glycerol, phenol, high concentration tetracaine or a mixture

of lignocaine and streptromycin.44 45 121 131 In all, the

average reported pain relief is measured in months and

many of these methods are associated with a high number of

initial failures. From the existing literature, it is dif®cult to

draw conclusions as to their true ef®cacy, but it is doubtful

whether they ever provide long-lasting bene®t. Authors

advocating the use of these measures frequently quote

failure rates or complications from other, more invasive

treatments that do not accurately re¯ect the current litera-

ture.

Pharmacotherapy

In general agreement, pharmacotherapy remains the main-

stay of treatment of TGN despite the fact that only few

randomized controlled trials have been conducted.35 142

Carbamazepine has been compared with placebo in three

separate studies, involving a total of 151 patients24 65 98 with

a good initial effect in approximately 70%. The NNT

(number-needed-to-treat) for effective pain control (>50%

pain relief compared with placebo) from these three studies

is 2.6, while NNH (number-needed-to-harm; i.e., adverse

effects in excess to those seen with placebo) is about 3.4.87

These studies, and its subsequent wide-spread use in TGN,

made carbamazepine something of a gold standard against

which other drugs have been compared in subsequent

controlled trials. These drugs include tizanidine, baclofen,

Table 4 Summary of drugs commonly used in TGN. Comments: CBZ, over 90% will respond initially (within 48 h),141 licensed in UK for TGN; PHT,

licensed in UK for TGN, narrow therapeutic range, i.v. treatment possible, therapeutic effect lost quickly, no randomized controlled trials; OXC, licensed for

TGN in some countries (not UK), effect similar to CBZ, but better tolerated, cross-allergy with CBZ in 25% cases; LTG, combination therapy with CBZ only

shown effective, slow dose escalation with fortnightly dose increments; BAC, best suited for combination therapy, do not withdraw quickly (risk of

convulsions)

Drug Initial dose Maintenance dose Adverse effects

Carbamazepine24 65 98 (CBZ) 200 mg day±1 400±1200 mg day±1 Sedation, dizziness, cognitive impairment,

headache, GI symptoms, allergic rash, leucopenia,

folate de®ciency, hyponatremia, several

drug interactions, warfarin!

Oxcarbazepine137 (OXC) 300 mg day±1 600±1200 mg day±1 Better tolerated than CBZ, sedation, dizziness,

cognitive impairment, hyponatremia, rash

Phenytoin14 (PHT) 300 mg day±1 200±400 mg day±1 Sedation, ataxia, behavioural change, cognitive

impairment, lymphadenopathy, osteopenia,

acne, gingival hypertrophy, rash, folate de®ciency, liver

failure, several drug interactions

Lamotrigine139 (LTG) 25±50 mg day±1 200±400 mg day±1 Allergic rash (necessitates immediate discontinuation),

sedation, dizziness, headache, ataxia, signi®cant interactions

with other anticonvulsants

Baclofen37 (BAC) 10 mg day±1 30±80 mg day±1 Sedation, ataxia, fatigue, GI symptoms, muscle weakness

TGN±pathophysiology, diagnosis and current treatment

127

pimozide, tocainade, and oxcarbazepine.37 77 82 130 137

While none have been shown to be superior to carbamaze-

pine, the small number of patients evaluated in individual

trials (usually less than 20) precludes ®rm judgement in this

regard. Table 4 lists the drugs most commonly used in this

condition.

Considering the complexities of the pathophysiology

of TGN (atypical TGN included) and the narrow

mechanism of action of the drugs available, combination

treatments seem a natural choice. However, there are no

published studies comparing directly polytherapy with

monotherapy.

The long-term effects of carbamazepine have been

evaluated in one study only, showing either loss of

effect or problems with tolerability in one half of

patients over 10 yr.128 Loss of effect can be compen-

sated to a degree by adding lamotrigine.139 However,

lamotrigine poses the problem of slow dose escalation,

which may be inconvenient to a patient with sudden

increase in TGN pain.

Baclofen alone seems to have a moderate effect on

TGN only, and its long-term ef®cacy remains in

doubt.37 One weak study suggests that clonazepam is

of value but, in our hands, it has been disappointing as

most patients with good initial response quickly

recognize that the effect is lost.23 Anecdotally, several

patients have been treated by ourselves with the

combination of carbamazepine or lamotrigine and

gabapentin. Doses needed are usually in the low-to-

moderate range (carbamazepine 400±800 mg day±1;

lamotrigine 200±400 mg day±1; gabapentin 900±1200

mg day±1), which are usually well tolerated by patients,

and preferred to monotherapy with high doses of

carbamazepine alone.

Using these drugs requires a good understanding of their

pharmacokinetics, metabolism, and interactions. There are

several good reviews available.34 141

Which treatment to choose ®rst?

With considerable amount of information about TGN

readily available, many patients and their relatives are

keen to consider surgery as ®rst-line treatment, in anticipa-

tion of a permanent cure. It is, therefore, imperative for the

doctor to have an understanding of the relative ef®cacy of

various treatments, including complications and recurrence

rates. Our policy is to view requests of early surgical

treatment with sympathy, even if the patient responds well

to pharmacotherapy, but to ensure that he has a realistic

view of what it entails.

Table 5 summarizes our current thinking with respect to

preferred treatments in individual cases. We emphasize that

it re¯ects only our experience and conclusions we have

drawn from the often con¯icting literature. As long as there

is no evidence-based medicine to guide treatment choice,

the doctor will have to combine theory with clinical

experience in as balanced a way as possible.

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(a) New cases

TGN typical/MRTA +ve +++ ++² ++ +² ++(+)

/MRTA ±ve ++ ++² ++ +² ++

TGN atypical/MRTA+ve + +² ++ ± ++

/MRTA ±ve ± +² ? ± +

Trigeminal neuropathy/MRTA+ve (+) ± ± ± +

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(b) Recurrence of pain

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/MRTA ±ve + ++² ++ +² ++

TGN atypical/MRTA +ve + +² ? ± ++

/MRTA ±ve ± +² ? ± +

TGN atypical/major sensory loss ± ± ± ± +

Trigeminal neuropathy/MRTA +ve (+) ± ± ± +

/MRTA ±ve ± ± ± ± +

Nurmikko and Eldridge

128

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