Neuropathic Pain II:

TRIGEMINAL NEURALGIA
Hanzara Panol
Objectives:
• Discuss classification, etiology, pathophysiology, clinical
characteristics, and differential diagnosis of trigeminal neuralgia(TN)
• Discuss medical( AEDs, Botox)and surgical management options
• Discuss laboratory tests necessary to monitor Antiepileptic Drugs
(AED)
• Discuss the imaging techniques available for the diagnosis of TN.
• Discuss the clinical presentation of pretrigeminal neuralgia
 Classification
• Trigeminal neuralgia (TN) is defined by recurrent unilateral brief
electric shock-like pain that is abrupt in onset and termination.
• The pain is restricted to one or more of the trigeminal divisions and is
triggered by innocuous sensory stimuli.
• TN is divided into either classical TN (CTN) or second-ary TN (STN)
caused by multiple sclerosis or a space occupying lesion such as a
tumor, cerebral aneurism or a megadolicho basilar artery.

Maarbjerg, et al., 2017

Maarbjerg, et al., 2017
 Etiology
• 1934, Dandy proposed that in at least 30% of TN patients the pain was caused by
a blood vessel compressing the trigeminal nerve
• Neurovascular conflict with compression.
• ‘‘transition zone’’ represents a particularly vulnerable area to, for example,
pressure from a blood vessel.

Maarbjerg, et al., 2017

Etiology
• Morphological changes of the trigeminal nerve
• Distortion
• Dislocation
• distension
• Indentation
• flattening

Maarbjerg, et al., 2017

Etiology
• There are numerous neurophysiological, neuroimaging and
histological studies pointing to focal demyelination of primary
trigeminal afferents near the entry of the trigeminal root into the
pons as the underlying pathophysiological mechanism in TN.

• Focally demyelinated primary afferents become hyperexcitable when

demyelination reaches such a level that ions can move in and out of
the axon, also away from the Ranvier node zones, at which point the
axons do not have enough energy to promptly reestablish the resting
potential.

Maarbjerg, et al., 2017

• Dependent on the specific structural lesion
• MS plaque affecting the trigeminal root
• Space occupying lesion in the cerebellopontine cistern such as
• epidermoid tumours
• Meningiomas
• Neurinomas
• arteriovenous malformations
• aneurysms

Maarbjerg, et al., 2017

Etiology and pathophysiology
• Demyelination of primary sensory trigeminal afferents in the root
entry zone is the predominant pathophysiological mechanism.
• In a significant proportion of the patients, the demyelination is caused
by a neurovascular conflict with morphological changes such as
compression of the trigeminal root.
• There are also unknown etiological factors, as only half of the CTN
patients have morphological changes.
• STN is caused by multiple sclerosis or a space-occupying lesion
affecting the trigeminal nerve.

Maarbjerg et al, 2017

Symptomatology

• tic douloureux characteristic wince that TN patients may exhibit at

a pain paroxysm
• Pain is extremely painful, sudden, unexpected, and short-lasting
pain paroxysm.
• Quality is stabbing, electrical shock-like, or shooting.
• Pain paroxysm may only last a fraction of a second, may recur, after a
refractory period, many times a day, and they may come in a series of
attacks with paroxysms close together.
• ½ TN patients also have continuous pain, aching, dull or burning
background pain of lower intensity in the same area.

Maarbjerg et al, 2017

Symptomatology
• Many patients experience a refractory period after a paroxysmal
attack where new attacks cannot be elicited.
• It has been proposed that it is caused by hyperpolarisation of the
sensory neuron
• It is highly characteristic that pain is triggered by innocuous sensory
stimuli
• light touch
• Talking
• Chewing
• brushing teeth
• cold wind against the face
Maarbjerg et al, 2017
Symptomatology
• TN most frequently affects the 2nd and/or 3rd trigeminal division
• Right side is slightly, but significantly, more often affected than the
left side.
• Bilateral TN is very rare in classical TN, and should raise suspicion of
secondary TN.
• TN is unpredictable periods of complete remission that may last
months or even years.
• Autonomic symptoms such as tearing and rhinorrhea have not been
associated with TN
Diagnosis
• Facial pain paroxysms triggered by innocuous stimuli constitute a
hallmark sign of trigeminal neuralgia
• Triggered pain is an essential criterion for the diagnosis of trigeminal
neuralgia
• Aim:
• How frequently triggers are present
• Which maneuvers activate them
• Where cutaneous and mucosal trigger zones are located.

Di Stefano et al., 2017

Diagnosis
• Collected clinical characteristics focusing on trigger factors were from
140 patients with TN
• Cross-sectional study
• Provocation of paroxysmal pain by various trigger maneuvers was
reported by 136 of the 140 patients.
• The most frequent maneuvers were gentle touching of the face (79%)
and talking (54%).
• Trigger zones were predominantly reported in the perioral and nasal
region.
Di Stefano et al., 2017
 Ignition hypothesis
• The ignition hypothesis of trigeminal neuralgia:
• Understanding of abnormal electrical behavior in injured sensory neurons.
• New histopathologic observations of biopsy specimens from patients with
trigeminal neuralgia who are undergoing microvascular decompression
surgery.
• Hypothesis: trigeminal neuralgia results from specific abnormalities of
trigeminal afferent neurons in the trigeminal root or ganglion.
• Injury renders axons and axotomized somata hyperexcitable.
• The hyperexcitable afferents, in turn, give rise to pain paroxysms as a
result of synchronized after discharge activity.
•
Devor et al., 2002
Differential diagnosis
• Trigeminal autonomic cephalalgias
• Posttraumatic or postherpetic pain
• Other facial pains.

Maarbjerg et al, 2017

 ‘‘pre Trigeminal neuralgia’’

• TN patients with persistent pain at onset, previously termed PTN

• An atypical initial manifestation that, in some patients, precedes the
classic presentation of TN, was introduced by Symonds.
• Continuous, aching pain in the upper or lower jaw, that later
developed into classic paroxysmal pain.
• Mitchell termed this pain as “pretrigeminal neuralgia” (PTN).

Evans et al., 2005

PTN
• Descriptions of PTN have included pain that is mild to moderate in
intensity, dull, aching, burning, throbbing, soreness of gums, and
toothache.
• When localized to a tooth, PTN must be differentiated from pain of
dental origin.
• In the absence of obvious clinical signs and of dental pathosis,
irreversible dental procedures must be deferred and the pain history
carefully reexamined.

Evans et al., 2005

Diagnosis of PTN
• Hindered by the atypical symptoms and is not made until paroxysmal
pain develops.
• Unexplained history of dull aching or burning pain that is recurrent
and/or provokable by non-noxious stimulus warrants further
investigation.
• The recognition of the dull, continuous, aching pain in the upper or
lower jaw as PTN, and the understanding that it may precede the
characteristic paroxysmal attacks of typical TN, expedites successful
treatment.
• Appropriate medications may relieve the pain and unnecessary
invasive and irreversible dental procedures may be avoided.1
Evans et al., 2005
PTN
• Fromm and Graff-Radford described the progression from PTN to TN
as progressive in weeks to years.
• The age distribution ranged from 22 to 81 years with a mean age of
56.2 years.
• There was no difference related to gender
• Pain occurred equally on the left and right sides.

Evans et al., 2005

Maarbjerg, et al., 2017
Graff-Radford et al., 2015
Graff-Radford et al., 2015
Multiple Sclerosis
• Trigeminal neuralgia occurs in 1–2%of multiple sclerosis (MS)
patients.
• Single most common entity leading to trigeminal neuropathy.
• When trigeminal neuralgia occurs bilaterally (4 % of patients), the
presence of MS is very high.
Multiple Sclerosis
• In the acute inflammatory or active phase, lesions may show low to
intermediate signal intensity on T1W images, high signal intensity on
long TR sequences (PD, T2W, and FLAIR), and enhancement after
intravenous administration of gadolinium contrast.
• In the chronic phase, lesions become hypo intense on T1W and hyper
intense on long TR sequences without enhancement after gadolinium
administration
Brainstem Gliomas
• Gliomas may involve the trigeminal nuclei
but rarely present with isolated TGN
deficits and are usually associated with
complex neurological syndromes.
• Brainstem gliomas are often infiltrative and
low grade with variable enhancement after
contrast medium administration.
• Similarly, metastases and lymphoma may
also cause cranial nerve V dysfunction but
are rarely the initial manifestation of
disease.
Vascular Lesions
• An infarct of the posterior inferior cerebellar artery (PICA) may affect
the dorsal trigeminal nucleus and tract but rarely manifest solely with
trigeminal neuropathy.
• It may be seen with more of a Wallenberg syndrome or lateral
medullary clinical presentation.
• In acute stages, infarcts present with subtle T2 and FLAIR
prolongation and restriction to water diffusion on DWI.
Cavernous Angiomas
• Susceptibility weighted (SWI) and T2* weighted imaging is well suited
to demonstrating blood degradation products, due to their presence
of hemosiderin.
• Cavernous hemangiomas manifest on MR as B popcorn shaped
lesions heterogenous in signal intensity on both T1 and T2 Wimages.
• Blood containing lesions are markedly hypo intense on T2* with a B
blooming effect (7a).
• They almost never enhance unless when associated with a venous
hemangioma
• Compression: Neural compression at bony foramina due to fibro-
osseous conditions such as fibrous dysplasia and Paget’s disease.
• Trigeminal schwannomas:
• CT isodense to slightly hypodense to brain parenchyma with variable
enhancement on postcontrast images.
• Large tumors tend to be more heterogenous reflecting cystic degeneration,
necrosis and internal hemorrhage.
• Tumors tend to be oblong in shape since they tend to follow the long axis of
the nerve.
• CT may depict bone remodeling or erosion
Fractures

• Nerve injury- compression, contusion, or

disruption
• Fractures of the superior orbital rim,
orbital roof, and superior orbital fissure
may injure the superior orbital and
ophthalmic nerve
• Central skull base fractures, extending
through the foramen rotundum, the
inferior orbital rim, or the pterygoid plates
may all affect V2 or its branches.
• Fractures travelling through the foramen
ovale, mandibular neck, and mandibular
body may injure the mandibular nerve or
the inferior alveolar nerve
Hardware—implants, plates, screws, scialastic
Persistent idiopathic facial pain
• The prevalence of neurovascular conflict is similar to that found in
asymptomatic nerves
• Neurovascular conflict should be considered a normal neuroanatomic
variant in patients with facial pain not fulfilling the TN diagnostic
criteria.