Trigeminal neuralgia (TN), a neuropathic pain syndrome, is defined by the International Association for the Study of Pain as “a sudden and usually unilateral severe brief stabbing recurrent pain in the distribution of one or more branches of the trigeminal nerve 1).
Also known as prosopalgia, or Fothergill's disease.
It has been described as among the most painful conditions known to mankind.
Trigeminal neuralgia is a relatively common neurosurgical pathology
The incidence of trigeminal neuralgia is 4.3 per 100,000 persons per year, with a slightly higher incidence for women (5.9 per 100,000) compared with men (3.4 per 100,000). 2)
In a majority of cases, TN symptoms begin appearing more frequently over the age of 50, although there have been cases with patients being as young as three years of age. It is more common in females than males.
One, two, or all three branches of the nerve may be affected.
10-12% of cases are bilateral (occurring on both the left and right sides of the face). Trigeminal neuralgia most commonly involves the middle branch (the maxillary nerve or V2) and lower branch (mandibular nerve or V3) of the trigeminal nerve, but the pain may be felt in the ear, eye, lips, nose, scalp, forehead, cheeks, teeth, or jaw and side of the face.
Trigeminal neuralgia can be subdivided according to the Burchiel scheme into trigeminal neuralgia types 1, 2a, and 2b. Such classification is important because it is predictive of surgical success.
Patients with type 1 TN experience a memorable onset of symptoms often described as a “lightning-bolt of pain that came out of nowhere.” The pain, while severe, tends to last for only seconds at a time and may occur many times per day. Even though attacks become more frequent, the pain is always shock-like and never constant or dull. Although attacks often occur spontaneously, patients with type 1 TN usually report certain triggering factors such as cold wind, eating, drinking, or using a washcloth. Additionally, patients with type 1 TN tend to have spontaneous remissions of symptoms lasting days to weeks early in the course of the disease with these pain-free intervals becoming shorter and less frequent as time passes. Patients with type 1 TN have the most favorable outcomes following any treatment modality.
In contrast, patients with type 2b trigeminal neuralgia have a more insidious onset of pain. Rather than experiencing a “lightning bolt out of nowhere,” patients may initially believe that they have a tooth or sinus ache for many months before the pain is determined to be neurologic. The pain is often described as being dull, boring, constant, aching, or throbbing. Like type 1 trigeminal neuralgia, the symptoms are extremely disabling. The prognosis following surgical treatment of patients with type 2b trigeminal neuralgia is less favorable than in patients with type 1 trigeminal neuralgia. However, patients who respond favorably to anticonvulsant medication may still benefit from an operation.
Type 2a trigeminal neuralgia is the diagnosis applied to patients who have type 1 symptoms early in the disease course and transition, over time, to a more constant pain consistent with type 2b trigeminal neuralgia. The outcomes of these patients following a surgical treatment is thought to be more favorable than in patients with type 2b trigeminal neuralgia but less favorable than in patients with type 1 trigeminal neuralgia.
Although the pathophysiology of idiopathic TN has not been fully elucidated.
The neurovascular compression is now considered an unquestionable dogma of idiopathic trigeminal neuralgia (ITN). However, there are more and more papers that provide information about other factors that promote such conflict or neuralgia itself.
The vessel that most often causes TN is the superior cerebellar artery (SCA), other known offending vessels include the anterior inferior cerebellar artery (AICA) and the vertebrobasilar trunk and vein.
Veins as the source of trigeminal neuralgias (TN) lead to controversies. Only a few studies have specifically dealt with venous implication in neurovascular conflicts (NVC).
A study shows the frequent implication of veins not only at TREZ but also at mid-cisternal portion and porus of Meckel cave 3).
Trigeminal neuralgia in pediatric patients is very rare. A case of typical trigeminal neuralgia in a child, demonstrating the pathogenesis of the neurovascular conflict due to subarachnoidal adhesions after meningoencephalitis was reported 4).
Other anatomical abnormalities have been considered, including differences of trigeminal nerve (TN) volume.
No correlation between volumetry and clinical data was detected 5).
The incidence rates of posterior fossa tumor-induced TN range from 2.1–11.6% percnt; in the literature; these cases mainly comprise meningiomas (14–54% percnt;), epidermoid tumors (8–64% percnt;), and vestibular schwannomas (7–31% percnt;) 6) 7) 8) 9).
Abarca et al. data support the theory that a small volume of the posterior fossa cisterns containing the trigeminal nerve may increase the incidence of ITN 10).
Horínek et al. did not find any association between the clinical neurovascular conflict (NVC) and the size of the posterior fossa and its substructures. MRI volumetry may show the atrophy of the affected trigeminal nerve in clinical neuromuscular conflict 11).
Park et al. did not find any volumetric differences (including the cisternal and parenchymal volumes) 12).
Chiari's malformation and hydrocephalus are rare associates of TN. The pathophysiology of TN in these cases may be due to neurovascular conflict, related to raised intracranial pressure from the hydrocephalus and/or the small posterior fossa volume in these patients. Drainage of associated hydrocephalus may be an effective surgical treatment 13).
High-resolution magnetic resonance imaging scans are able to demonstrate significant volumetric differences of the pontomesencephalic cistern in patients with unilateral TN. A smaller cistern may be correlated with the occurrence of a neurovascular compression, and these findings support the neurovascular compression theory in idiopathic TN 14).
Park et al. confirmed that small pontomesencephalic cistern volumes were more frequent in patients with TN 15).
The Visual Analog Scale (VAS) and the Barrow Neurological Institute Pain Scale (BNI-PS) are 2 of the most frequently employed patient-reported outcome (PRO) tools used by clinicians to rate pain for patients with trigeminal neuralgia (TN).
Reinard et al., from the Department of Neurosurgery, Henry Ford Medical Group (HFMG), and the Wayne State University School of Medicine, Detroit, Michigan, identify racial and socioeconomic disparities in the diagnosis and treatment of trigeminal neuralgia (TN), this appeared to stem from outside HFMG from a difference in referral patterns to the neurologists and neurosurgeons 16).
Trigeminal Neuralgia can be a typical symptom in cerebellopontine angle tumours like epidermoid, especially in young patients, so all the patients with trigeminal neuralgia should be investigated for lesion in cerebellopontine region 17).
Magnetic resonance imaging (MRI) can be helpful in visualizing neurovascular conflict (NVC) of the trigeminal nerve, but the relationship between these two events is controversial.
Although pharmacological therapy is the primary treatment modality for trigeminal neuralgia associated pain, ineffective analgesia and dose limiting side effects often prompt patients to seek alternative pharmacological solutions such as interventional nerve blockade.
The international guidelines on TN treatment recommend carbamazepine and oxcarbazepine as first line treatment based on clinical studies.
Other drugs used to treat TN have not been investigated to the same extent but some smaller studies showed promising results using pregabalin , lamotrigine , baclofen and gabapentin. In the international guidelines it is stated that “if any of these sodium-channel blockers (carbamazepine or oxcarbazepine, edt.) are ineffective, referral for a surgical consultation would be a reasonable next step” . However, the guidelines also state that “considering the relatively narrow mechanism of action of the available drugs (carbamazepine, edt.), combination treatments might be useful” .
Based on the clinical experience of Heinskou et al they agree with the international treatment guidelines although find that referral for neurosurgery after failed monotherapy may be too hasty and in general try out a combination treatment before referral to surgery. Unfortunately, the scientific support for combination treatment is sparse and there are no published studies directly comparing monotherapy with polytherapy.
They suggest that follow up on medical treatment should remain in the hands of experts until the condition is stable and the patient is familiar with the program of titrating up and tapering of medication according to the level of pain and side effects. They suggest that 2 years of follow up is appropriate, but this depends on the resources of the clinic and the health care system 18).
Microvascular decompression is a first-line neurosurgical approach for classical TN with neurovascular conflict, but can show clinical relapse despite proper decompression. Second-line destructive techniques like radiofrequency thermocoagulation have become reluctantly used due to their potential for irreversible side effects. Subcutaneous peripheral nerve field stimulation (sPNFS) is a minimally invasive neuromodulatory technique which has been shown to be effective for chronic localised pain conditions.
The most frequently used surgical management of trigeminal neuralgia is Microvascular decompression (MVD), followed closely by stereotactic radiosurgery (SRS). Percutaneous stereotactic rhizotomy (PSR) , despite being the most cost-effective, is by far the least utilized treatment modality 19).
Radiosurgery is a well-established treatment modality for medically refractory trigeminal neuralgia. The exact mechanism of pain relief after radiosurgery is not clearly understood. Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results.
There is evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed and need to be explored in future studies 20).
The results suggest that stereotactic radiosurgery with linear accelerators could constitute an effective and safe therapeutic alternative for drug-resistant trigeminal neuralgia. However, existing studies leave important doubts as to optimal treatment doses or the therapeutic target, long-term recurrence, and do not help identify which subgroups of patients could most benefit from this technique 21).
Trigeminal neuralgia (TN) recurring after surgery can be difficult to treat. Treatment algorithms have not been standardized or universally accepted.
The records of 22 patients (13 M and 9 F) suffering recurrent TN after one (2 gamma knife surgery, 5 percutaneous radiofrequency rhizotomy, 6 percutaneous retrogasserian glycerol rhizotomy, 3 microvascular decompression) or more (6 patients) procedures were reviewed. Seven patients had TN related to multiple sclerosis (MS). Mean follow-up was 51.81 ± 26.63 months. 81.81 % of patients reported an acute pain relief. No major complication was observed after PBC. Eight patients (36.36 %) experienced pain recurrence and underwent one (five patients) or more (three patients) PBC. At the last follow-up, we obtained an excellent outcome (BNI I-II) in 16 patients out of 22 (72.72 %) and a good outcome (BNI III) in the remaining six. No patients had an uncontrolled pain. The lack of history of MS (p = 0.0174), the pear-like shape of the balloon at the operation (p = 0.0234) and a compression time <5 min (p < 0.05) were associated to higher pain-free survival. Considering these results PBC could be considered a useful technique for patients whose pain recurs after other procedures 22).
Although no procedure is best for all patients, posterior fossa exploration PFE gives the operating surgeon the option of performing either a nondestructive (microvascular decompression) or destructive (partial sensory rhizotomy) procedure and is associated with better facial pain outcomes for this difficult patient group 23).
The study of Montano et al., shows no differences in the short term results among different procedures for TN in MS patients. Each technique demonstrate advantages and limits in terms of long term pain, recurrence rate and complication rate. Each patient should be accurately informed on pros and cons of each procedure in order to be involved in the most appropriate choice 24).
Mortality rates for MVD (0.22%), rhizotomy (0.42%), and SRS (0.12%) were low 25).
Forty-three patients with trigeminal neuralgia were recruited, and diffusion tensor imaging was performed before radiofrequency rhizotomy. By selecting the cisternal segment of the trigeminal nerve manually, they measured the volume of trigeminal nerve, fractional anisotropy, apparent diffusion coefficient, axial diffusivity, and radial diffusivity. The apparent diffusion coefficient and mean value of fractional anisotropy, axial diffusivity, and radial diffusivity were compared between the affected and normal side in the same patient, and were correlated with pre-rhizotomy and post-rhizotomy visual analogue scale pain scores. The results showed the affected side had significantly decreased fractional anisotropy, increased apparent diffusion coefficient and radial diffusivity, and no significant change of axial diffusivity. The volume of the trigeminal nerve on affected side was also significantly smaller. There was a trend of fractional anisotropy reduction and visual analogue scale pain score reduction (P = 0.072). The results suggest that demyelination without axonal injury, and decreased size of the trigeminal nerve, are the microstructural abnormalities of the trigeminal nerve in patients with trigeminal neuralgia caused by neurovascular compression. The application of diffusion tensor imaging in understanding the pathophysiology of trigeminal neuralgia, and predicting the treatment effect has potential and warrants further study 26).
Between January 2003 and December 2013, 360 patients with idiopathic TN and 39 patients with tumor-related TN who had undergone microsurgery were retrospectively studied. Kaplan-Meier survival curves were generated and compared by Log-rank test, and the possible prognostic factors were analyzed by the Cox proportional-hazards regression.
Patients with tumor-related TN exhibited a younger age of pain onset (46.28 ± 18.18y vs. 53.03 ± 11.90y, p = .006), a briefer symptom duration (3.20 ± 4.38y vs. 7.01 ± 6.04y, p = .000), and much more preoperative neuropathic deficits (61.54 vs. 24.17, p = .000), as compared with patients with idiopathic TN. Using Kaplan-Meier analysis, we found microsurgery was effective in 72.3% of patients with idiopathic TN, and in 86.4% of cases with tumor-related TN at six years follow-up postoperatively. Prognostic analysis suggested that a clear-cut neurovascular compression in patients with idiopathic TN (HR = 3.098, 95%CI: 1.800-5.311; p = .000) and total tumor removal in patients with tumor secondary TN (HR = 7.662, 95%CI: 0.098-36.574; p = .044) were positively correlated with excellent long-term outcomes.
The occurrences of TN at younger age, a shorter duration and preponderance of preclinical neuropathic symptoms are the characteristics of TN patients secondary to intracranial tumor, in contrast to patients with TN caused by a compressed vessel. Microsurgery is an effective and safe treatment modality for TN regardless of the disease etiology, the involvement of a clear-cut vascular offender and total tumor resection are the most important predictors of excellent outcome for microsurgery in idiopathic and tumor-related TN patients, respectively 27)