Atypical trigeminal neuralgia: role of neurophysiological tests for diagnosis - Pathos

Trigeminal neuralgia is the most frequent non-odontogenic facial pain in people over fifty. Its annual incidence ranges from 4 to 29 cases per 100.000 population. The prevalence is between 0.16% and 0.3%. The incidence is higher in women than in men, 3:2, and increases with age. Although very rare, children and adolescents may be affected.

Trigeminal neuralgia is usually easy to diagnose, at least in its typical form. It is characterized by paroxysmal pain crises of short duration (a few seconds to a maximum of two minutes), strictly in the trigeminal territory. Pain is often described as excruciating or electric-shock-like, very intense and triggered by harmless tactile facial stimuli: washing the face, shaving, applying makeup, brushing teeth, chewing; even a puff of air on the face can trigger the crises. Typically, the neurological examination is negative.

Three forms are distinguished:

-Classical or typical or type 1 (caused by neurovascular conflict, NVC);

-Secondary or atypical or type 2 (caused by a demyelinating disease such as multiple sclerosis or by neoformations, usually benign, such as meningiomas or neurinomas, or by arteriovenous malformations);

-Idiopathic of unknown cause.

Each of the three forms, but especially the classic and idiopathic forms, may present only with paroxysmal pain crises or with continuous background pain between crises.

Atypical presentations comprise less than 40% of trigeminal neuralgia cases and pose greater diagnostic challenges than typical cases as they require differentiation from other facial pain conditions. 1-4

Trigeminal neuralgia is diagnosed exclusively through clinical evaluation, as laboratory and imaging tests are not definitive. Neurovascular conflict detected via MRI must be associated with the patient's clinical symptoms to establish its significance.5,6

In case of atypical trigeminal neuralgia, one of the most common and intricate differential diagnoses is post-traumatic trigeminal painful neuropathies (PTTN), which often arise from minor dental procedure like root canal treatment or avulsion of some dental elements.

Pain, frequently persistent and aching, is accompanied by negative (hypoesthesia and/or hypoalgesia) or positive (hyperalgesia and/or allodynia) somatosensory symptoms. The latter are not specific for neuropathy. In some cases, persistent dento-alveolar pain (PDAP) with or without somatosensory changes may also be in the differential diagnosis, and some signs and symptoms overlap with the diagnostic criteria for PTTN.  In intraoral forms of PTTN, in contrast to extraoral forms, the objective finding of neurological changes is difficult; neurological changes could be a diriment diagnostic criterion toward trigeminal neuralgia.1,7-9 In these cases, the use of neurophysiological tests such as blink reflex, for example, can reveal an altered conduction velocity along the trigeminal nerve and thus its functional alteration. This reflex is usually within the normal range in classic and idiopathic forms of trigeminal neuralgia.

The blink reflex technique consists of recording the blink motor response obtained by electrical stimulation of the orbital region. The supraorbital nerve (which heads the first trigeminal branch) is stimulated with single electrical pulses, and motor responses are recorded at the orbicularis of the eyelids bilaterally mediated by the facial nerve.10-12

Being able to make a correct differential diagnosis between trigeminal neuralgia and trigeminal neuropathy is very important because the therapeutic approach is different, both pharmacologically and invasively.13

The most appropriate drugs for neuralgia are sodium channel blockers such as carbamazepine; for neuropathy, calcium channel blockers such as gabapentinoids and tricyclic antidepressants such as amitriptyline.13-15

if there is no response to treatment, for trigeminal neuralgia, regardless of the cause, radiofrequency thermorhizotomy, or other neurolesions are an appropriate choice for trigeminal neuralgia, whatever the cause. In cases of trigeminal neuropathy, these techniques are strongly discouraged because they may worsen the clinical presentation.16,17

The 66-year-old female patient presented with left facial pain began in 2014, when a late complication caused by dental implant placement. The complication in question was the corrosion of the left maxillary sinus floor by implant pins. To rectify this, the patient underwent surgical intervention to repair the sinus lesion and implant removals. Additionally, a release plate (byte) is also made. A period of well-being of about 6 months follows, then intense pain returns (NRS 8-9). The patient has reported continuous and dull pain since onset. Pain was spontaneous but also provoked by light touch of the nose or lip, referred intra- and extra-orally to both the mandible and maxilla; Additionally, there is also muscle contracture of the ipsilateral masseter. Despite benzodiazepine use, pain is present 24 hours a day and prevents sleep. The neurological examination shows normal results. She commences treatment with NSAIDs, steroids and muscle relaxants, substituting various forms of medication, but experiences persistent burning pain. Nevertheless, she experiences intermittent episodes of electric shock pain, occurring in addition to the underlying urethral pain, leading to the addition of carbamazepine to her therapy.

There is an initial reduction in pain, but the drug is discontinued because of the appearance of skin reactions. Other anticonvulsants (gabapentin, pregabalin) are administered in addition to opioids and acetaminophen, but without any improvement. With amitriptyline, the patient reports partial pain relief, as well as cannabis and tapentadol.

The pain improves over time and periodically disappears for two to three months. These treatments are prescribed by several specialists consulted by the patient. Neurologists, neurosurgeons, pain therapists, and dentists are frequently consulted for treatment. Additionally, several bytes have been inserted on at least five occasions, but subsequently removed due to deteriorating symptoms. A mobile and skeletonized prosthesis has been constructed to provide stability and enable chewing; however, oral pain currently inhibits this functionality.18
Trigeminal neuropathy and atypical facial neuralgia are the most commonly diagnosed conditions. However, if symptomatology is enriched by paroxysmal electric-shock component, a study of encephalic MRI with angiographic sequences and ponto-cerebellar angle is requested.

Examination reveals an abnormality in the course of the left superior cerebellar artery (SCA) in contact with the intracisternal tract of the left trigeminal nerve. At the point of contact, the nerve is observed to be slightly bent downward. This finding indicates a diagnosis of trigeminal neuralgia due to neurovascular conflict, suggesting the need for microvascular decompression surgery. However, the patient declines the surgery due to its invasive nature. We advise exercising caution when taking lamotrigine, as it can cause severe skin reactions that may lead to discontinuation of the medication, similar to carbamazepine.

The patient was observed at this stage. To confirm the diagnosis, a blink reflex test was proposed, which showed normal results. Based on the clinical manifestations, diagnostic criteria of type 2 or atypical trigeminal neuralgia, lack of response to pharmacological interventions, and severe and worsening pain causing impaired psychophysical functioning (including difficulties in speaking, eating, and brushing teeth), we propose neurolesion with continuous radiofrequency (percutaneous retrogasserian root thermophysiotomy) after a thorough discussion of potential risks and limitations with the patient.

To carry out the procedure, the patient is transferred to the operating room. A peripheral vein is cannulated and ECG, non-invasive blood pressure, and peripheral oxygen saturation are monitored. The procedure is conducted under intravenous sedoanalgesia administered by the anesthesiologist.

Using radiological control (C-arm ), the foramen ovale is highlighted, and through a special RF needle (10 cm length, 21 G gauge, and 5 mm exposed tip), to reached and pass through to the trigeminal cistern in the retrogasserian location (as evidenced by CSF leakage from the needle). Electrodiagnostic testing is performed by adjusting the needle position until sensitive paresthesias are evoked in the range of 0.1 V to 2.5 V and avoiding eliciting masseter clonias.

The procedure involved performing a first lesion at an angle of 60° for 60 seconds. However, after finding it ineffective, two more lesions were performed at 70° for 75 seconds each. The results of hypoalgesia and nuanced tactile hypoesthesia were then evaluated to predict a satisfactory antalgic result, and no intraoperative complications were recorded.  In the following days after the operation, the patient reported a gradual decrease in pain and a reduction in medication. One week later, the patient stated that the pain had completely disappeared without medication. However, a faint and nuanced tactile hypoesthesia was still present in the treated areas, specifically the second and third branches of the left trigeminal nerve, as anticipated.

The clinical case reported is frequently encountered in orofacial pain centres. Urgent and persistent facial pain for most of the day, spontaneous but also provoked, intra- and extra-oral, and occurring with a reasonable time interval after several dental treatments (even successful ones) in the same area of invasive treatments in a woman between the fifth and sixth decades of life, is quite pathognomonic of a post-traumatic painful trigeminal neuropathy (PTTN) in which the trauma is represented by dental procedures8. In fact, idiopathic persistent dentoalveolar pain (PDAP), formerly known as atypical odontalgia or phantom tooth pain, can also be included in the differential diagnosis. However, in the latter, the temporal relationship between the trauma and the onset of symptoms may not be clear, and any somatosensory changes may extend outside the area of trigeminal innervation. In our case there was no somatosensory sign, either positive or negative, but this finding unfortunately combines trigeminal neuralgia, intraoral PTTN and PDAP without somatosensory signs. To date, PDAP has been classified by the International Classification of Orofacial Pain (ICOP) as idiopathic rather than neuropathic, although there is much evidence to suggest neuropathy.1,9,14

A criterion that is sometimes used empirically to make a diagnosis of trigeminal neuralgia is the response to sodium channel blockers, especially carbamazepine, because it controls pain in more than 90 per cent of cases. In the present case, this could not be assessed because of the early onset of severe skin reactions following its use, which forced early discontinuation of therapy. The same phenomenon has been reported with lamotrigine.13,15

Our patient reported electric shocks (typical of trigeminal neuralgia), but these were continuous and prolonged, very different from the brief paroxysms of neuralgia.

Pain caused by light touch, as in our case, can also occur in PTTN and is typical of trigeminal neuralgia.

On the other hand, long spontaneous remissions are characteristic of trigeminal neuralgia, although recurrences also occur in PTTN.13

Unfortunately, imaging does not make a decisive contribution in these cases, since both the absence and the presence of neurovascular conflict (in our case more contact than real conflict) do not resolve the diagnostic doubt. In fact, the high sensitivity of imaging is not accompanied by such a high specificity, since the detection of changes without clinical relevance is not uncommon. Furthermore, the normality of the imaging data does not in itself allow the exclusion of possible organic lesions, since MRI, although capable of high structural resolution, does not allow the exclusion of pathologies of certain structures at the cellular or subcellular level, as may be the case in some forms of neuropathy.19

The role of neurophysiological studies, functional studies par excellence, then becomes essential, and in the orofacial district the gold standard is the blink reflex, or blink reflex. An abnormal reflex has a sensitivity of 94% and a specificity of 87% in detecting secondary trigeminal neuralgia. This is the same as MRI. The blink reflex is also useful in detecting neuropathic facial pain.

Especially when this finding is placed in clinical context. In general, a normal blink reflex excludes the presence of neuropathic damage to the main branches of the trigeminal nerve, whereas it is less reliable for assessing damage to terminal branches such as the lingual or inferior alveolar nerve. Conversely, an altered reflex generally rules out classic or idiopathic trigeminal neuralgia. These techniques have been considered effective and recommended in recent guideline reviews in the 2009 Eropean Federation of Neurological Societies (EFNS) and the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP).20,21

The blink reflex is a dependable and hassle-free test, widely adopted by neurophysiology centers.

In contrast, more elaborate tests like quantitative sensory testing (QST), laser evoked potentials (LEPs), or skin biopsies lack the same standing. Nevertheless, LEPs applied to the trigeminal region are found useful in detecting sensory pathologies related to the orofacial area. LEP alterations are observed in secondary trigeminal neuropathies, whereas abnormalities are evident in 40-50 percent of idiopathic trigeminal neuralgia. This implies that dysfunction in the A-delta circuit has a role in the development of neuralgic pain. LEPs are more sensitive than trigeminal reflexes and can help identify underlying pathological mechanisms.19,22

Our case report illustrates the diagnostic challenges of non-odontogenic orofacial pain and how these challenges affect appropriate therapeutic decisions.

Initially, pain resembled post-surgical neuropathy, whereas later it developed into atypical trigeminal neuralgia. It is possible that it was initially atypical trigeminal neuralgia, but the constant burning pain disguised it. Consequently, what is the correlation between dental treatment and the development of a condition that is primarily caused by the compression of a demyelinated nerve root tract?

Functional tests provided a response that, when accurately placed in the multifaceted clinical picture, facilitated an effective therapeutic decision.

It is recommended that such tests are incuded in the diagnostic protocol of every medical specialist.