Portal de Periódicos da CAPES

Trigeminal neuralgia

2016; Elsevier BV; Volume: 16; Issue: 10 Linguagem: Inglês

10.1093/bjaed/mkw015

2058-5357

C K Vasappa, Shitij Kapur, H Krovvidi,

Facial Nerve Paralysis Treatment and Research

Key points•Trigeminal neuralgia (TN) is a relatively rare but debilitating facial pain condition.•Classical TN occurs without any apparent cause other than possible microvascular compression.•TN is a clinical diagnosis, but MRI is helpful to exclude secondary causes.•Many patients respond to pharmacological therapy and carbamazepine remains the first-line drug.•Microvascular decompression has the best outcome in terms of quality and duration of pain relief. •Trigeminal neuralgia (TN) is a relatively rare but debilitating facial pain condition.•Classical TN occurs without any apparent cause other than possible microvascular compression.•TN is a clinical diagnosis, but MRI is helpful to exclude secondary causes.•Many patients respond to pharmacological therapy and carbamazepine remains the first-line drug.•Microvascular decompression has the best outcome in terms of quality and duration of pain relief. Trigeminal neuralgia (TN) is a characteristic neuropathic pain involving the trigeminal nerve distribution. The International Association for the Study of Pain (IASP) defines TN as 'a unilateral painful disorder that is characterised by brief, electric shock like pains, is abrupt in onset and termination, and is limited to the distribution of one or more divisions of the trigeminal nerve'. The annual incidence of TN in the UK is around 26/100 000.1Zakrzewska JM Linskey ME Trigeminal neuralgia.BMJ Clin Evid. 2014; 10: 1207Google Scholar Worldwide prevalence varies from 10 to 300/100 000. The peak age of onset is between 50 and 60 yr with a male-to-female ratio of 1:2. In this article, we present a review of the pathophysiology, diagnosis, and treatment of TN based on available evidence. The exact aetiology and pathophysiology of TN remains to be clearly elucidated. According to the 'ignition theory' (the most common hypothesis), TN is the result of abnormalities in the afferent neurones of the trigeminal root or ganglion.1Zakrzewska JM Linskey ME Trigeminal neuralgia.BMJ Clin Evid. 2014; 10: 1207Google Scholar Any injury to the axons can make them hyperexcitable, leading to this painful neuropathic condition. It has been suggested that central sensitization also plays a role in TN. Some of the risk factors in developing TN are multiple sclerosis (MS), increased age, stroke, hypertension (in women), Charcot–Marie–Tooth disease, and tumours in the region of the trigeminal nerve root. In the majority of TN cases, the cause is thought to be demyelination of the trigeminal nerve root near its entry into the pons.2Zakrzewska JM Facial pain.in: Stannard C Kalso E Ballantyne J Evidence-based Chronic Pain Management. Wiley-Blackwell, Chichester, West Sussex2010: 144-148Crossref Scopus (2) Google Scholar This area (called the root entry zone) is where the peripheral myelin of Schwann cells meet the central myelin of the astrocytes. The area of nerve root that has been affected can spontaneously discharge impulses that trigger TN. A-β fibres (carrying touch sensation) lie in close proximity with A-δ and C fibres (carrying pain sensation) in the root entry zone, leading to ephaptic cross-talk between them. This might explain precipitation of attacks of TN by trivial tactile stimulation.1Zakrzewska JM Linskey ME Trigeminal neuralgia.BMJ Clin Evid. 2014; 10: 1207Google Scholar,3Love S Coakham HB Trigeminal neuralgia pathology and pathogenesis.Brain. 2001; 124: 2347-2360Crossref PubMed Scopus (563) Google Scholar The trigeminal ganglion itself can show pathological changes like hypermyelination.4Nurmikko TJ Eldridge PR Trigeminal neuralgia—pathophysiology, diagnosis and current treatment.Br J Anaesth. 2001; 87: 117-132Crossref PubMed Scopus (278) Google Scholar In many patients, the demyelination is caused by compression by a vascular structure. MS, tumours, and arteriovenous malformations can lead to primary demyelination. TN when associated with MS may show plaques of demyelination at the root entry zone. These patients present at a younger age and although do not tolerate anticonvulsants very well, their response to interventions is similar to patients with classical TN. The theory of vascular compression leading to TN has been supported by the results of surgical decompression and evidence from MRI and nerve conduction studies. However, vascular contact is not a consistent finding in all TN patients and cadaveric studies have shown vascular compression as an incidental finding in people who did not suffer from TN.4Nurmikko TJ Eldridge PR Trigeminal neuralgia—pathophysiology, diagnosis and current treatment.Br J Anaesth. 2001; 87: 117-132Crossref PubMed Scopus (278) Google Scholar TN is essentially a clinical diagnosis based on its characteristic presentation. A: Paroxysmal attacks of pain lasting from a fraction of a second to 2 min, affecting one or more divisions of the trigeminal nerve and fulfilling criteria B and CB: Pain has at least one of the following characteristics: Intense, sharp, superficial, or stabbing Precipitated from trigger areas or by trigger factorsC: Attacks are stereotyped in the individual patientD: There is no clinically evident neurological deficitE: Not attributed to another disorder Ref: NICE Clinical Knowledge Summaries: Trigeminal Neuralgia, December 2014. TN has to be differentiated from other causes of orofacial pain and headaches. Headache disorders: cluster headache, trigeminal autonomic cephalalgiaDental pain: cracked tooth, dental abscessTemporo-mandibular joint disordersOther neuralgias: occipital neuralgia, glossopharyngeal neuralgia, post-herpetic neuralgia, atypical facial painTumours: acoustic neuromas, meningiomasSinusitis TN is classified5The International Classification of Headache Disorders.Cephalalgia. 2013; 33 (3rd edition): 774-778Google Scholar as: (i)Classical TN—occurs without any apparent cause other than microvascular compression. It is further subdivided as: (a)purely paroxysmal: where the patient is pain free between attacks and(b)with concomitant persistent facial pain(also called as atypical TN or TN type 2): a low-grade background facial pain persists between the attacks. Central sensitization may account for the persistent pain. Neurovascular compression may not be demonstrable in this type and is resistant to several treatment modalities.(ii)Symptomatic TN—caused by another recognizable disorder that leads to neural damage (e.g. MS, herpes zoster, trauma, space-occupying lesion). TN is diagnosed on the basis of typical history and clinical features. Although there are no specific investigations to confirm the diagnosis, it may be necessary to undertake some to rule out symptomatic TN: (i)A neurological examination would help to detect any neurological deficit, area of involvement, and trigger areas. A sensory deficit, absent trigeminal reflexes, and bilateral involvement suggests symptomatic TN.6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar(ii)MRI scanning of the brain is useful to detect any secondary causes like MS or tumours. Routine neuroimaging may identify a cause in up to 15% of patients.6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar,7Han-Bing S Wei-Guo Z Jun Z Ning L Jian-Kang S Yu C Predicting the outcome of microvascular decompression for trigeminal neuralgia using magnetic resonance tomographic angiography.J Neuroimaging. 2010; 20: 345-349Crossref PubMed Scopus (29) Google Scholar High-resolution MRI may be able to identify vascular compression.2Zakrzewska JM Facial pain.in: Stannard C Kalso E Ballantyne J Evidence-based Chronic Pain Management. Wiley-Blackwell, Chichester, West Sussex2010: 144-148Crossref Scopus (2) Google Scholar,6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar(iii)Evoked potentials, quantitative sensory testing, and electrophysiological studies can also help detect symptomatic TN, but as yet do not have enough evidence to be routinely recommended.2Zakrzewska JM Facial pain.in: Stannard C Kalso E Ballantyne J Evidence-based Chronic Pain Management. Wiley-Blackwell, Chichester, West Sussex2010: 144-148Crossref Scopus (2) Google Scholar,6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar(iv)Preoperative magnetic resonance tomographic angiography has been suggested as useful in patient selection and outcome prediction for microvascular decompression (MVD).7Han-Bing S Wei-Guo Z Jun Z Ning L Jian-Kang S Yu C Predicting the outcome of microvascular decompression for trigeminal neuralgia using magnetic resonance tomographic angiography.J Neuroimaging. 2010; 20: 345-349Crossref PubMed Scopus (29) Google Scholar The trigeminal nerve is the fifth and largest cranial nerve and composed of both sensory and motor components. The sensory nuclei are present throughout the brainstem. It is a paired nerve and exits the lateral surface of pons bilaterally as separate sensory and motor roots. The sensory root forms the trigeminal (Gasserian) ganglion in the middle cranial fossa and is located in a cavity called Meckel's cave. This ganglion divides into ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves. The motor root passes along with the sensory root, but is distributed only to the mandibular division. The ophthalmic nerve exits the cranium through the superior orbital fissure and innervates the skin above the eye, forehead, and globe. The maxillary nerve exits the cranium through the foramen rotundum and supplies the skin between the eye and mouth. The mandibular nerve exits through the foramen ovale. Sensory fibres of V3 innervate the skin of the lateral part of the head and lower jaw, tongue, mucosa of oral cavity, and teeth. Motor fibres innervate the muscles of mastication. The trigeminal nerve, through its branches, carries parasympathetic supply to ganglia and the lacrimal glands (V1, V2), nasal glands (V2), submandibular, sublingual, and parotid glands (V3). Optimal pharmacotherapy should be the first line of treatment in the majority of patients with TN. Symptomatic TN needs to be managed by addressing the treatment of the causative condition. Carbamazepine (200–1200 mg) remains the drug of choice, with good evidence1Zakrzewska JM Linskey ME Trigeminal neuralgia.BMJ Clin Evid. 2014; 10: 1207Google Scholar of efficacy in TN and a number needed to treat of 1.8. It is an anticonvulsant drug that blocks the use-dependent sodium channels and may also prevent synaptic transmission in the trigeminal nucleus. The major limiting factor in its use is the high incidence of side-effects, including drowsiness, dizziness, rash, liver damage, hyponatraemia, and ataxia. Patients on carbamazepine should therefore have their liver function, blood count, and serum electrolytes checked at regular intervals. Oxcarbazepine, a derivative of carbamazepine, has a better side-effect profile and similar efficacy. Gabapentin, pregabalin, and amitriptyline are commonly used in TN because of their efficacy in treating neuropathic pain conditions; however, evidence of their effectiveness specific to TN is not strong. Baclofen and lamotrigine have been used as add-on therapy. Baclofen may be useful in patients with MS suffering from TN.1Zakrzewska JM Linskey ME Trigeminal neuralgia.BMJ Clin Evid. 2014; 10: 1207Google Scholar Similarly, phenytoin has been used with limited benefit in some cases of TN. Patients who fail to benefit from pharmacological therapy or experience significant side-effects should be considered for surgical interventions. These procedures can be carried out at three levels. Peripheral techniques involve neurolysis of the trigeminal nerve branches distal to the gasserian ganglion. This can be accomplished by using laser therapy, alcohol injections, or neurectomy. These procedures are less invasive than other surgical interventions, but the pain relief is short term, lasting 6 months to 1 yr. Patients may also develop dysesthesias post-procedure.6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar However, they can be useful in patients who are not fit for any other surgical interventions, or as an emergency procedure. The gasserian ganglion can be ablated using thermal (radiofrequency), chemical (glycerol, phenol, alcohol), or mechanical (balloon compression) techniques. A needle is passed percutaneously into the foramen ovale to reach the ganglion to facilitate these procedures. The procedure is usually performed under local anaesthetic and sedation, as the patient's co-operation is necessary. Fluroscopy-guided technique is more precise in localizing the foramen ovale. The patient is placed supine, with neck slightly extended. A submental view X-ray is obtained. Then, by gradually moving the C arm obliquely towards the affected side, the foramen ovale is located between mandibular process and maxilla. A needle is directed towards the foramen ovale using X-ray guidance (Fig. 1). Needle tip position is confirmed using lateral views (Fig. 2). Once the needle is in a satisfactory position, rhizotomy is achieved by radiofrequency, glycerol injection, or balloon compression.Fig 2Lateral view of needle in foramen ovale.View Large Image Figure ViewerDownload (PPT) These interventions provide longer duration of pain relief, lasting around 4–5 yr in 50% of patients.2Zakrzewska JM Facial pain.in: Stannard C Kalso E Ballantyne J Evidence-based Chronic Pain Management. Wiley-Blackwell, Chichester, West Sussex2010: 144-148Crossref Scopus (2) Google Scholar,6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar However, there is a high incidence of sensory loss and dysaesthesias, with around 4% developing anaesthesia dolorosa.6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar Balloon compression can lead to arrhythmias, aseptic meningitis, and temporary diplopia. (i)MVD: The trigeminal nerve in the posterior fossa is accessed by a suboccipital craniotomy. The nerve root is freed from vessels compressing it (most commonly superior cerebellar artery) and a teflon felt is placed between them. MVD has a very good initial success rate (80–90%) and provides the most sustained pain relief of all the procedures available. The relapse rate at the end of 10 yr is about 30–40%.8Eliav E Neuropathic orofacial pain.in: Tracey I PAIN 2012 Refresher Courses. IASP, Seattle2012: 263-265Google Scholar,9Barker FG Jannetta PJ Bissonette DJ Larkins MV Jho HD The long-term outcome of microvascular decompression for trigeminal neuralgia.N Engl J Med. 1996; 334: 1077-1083Crossref PubMed Scopus (1033) Google Scholar Since MVD is a major neurosurgical procedure, it is associated with a mortality of 0.5%. Other complications include aseptic meningitis (11%), hearing loss (10%), sensory loss (7%), cerebrospinal fluid leaks, haematomas, and infarcts. The complication rate is lower in centres that perform MVD regularly.(ii)Gamma knife stereotactic radiosurgery: is a destructive procedure that aims at delivering a focused beam of radiation to trigeminal nerve root in the posterior fossa where there is a proven vascular compression. MRI mapping is used to locate the exact site of microvascular compression. This procedure provides complete pain relief in up to 69% of patients by the end of 1 yr,6Gronseth G Cruccu G Alksne J et al.Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies.Neurology. 2008; 71: 1183-1190Crossref PubMed Scopus (407) Google Scholar but the benefits may not be sustained, although it can be repeated in recurrent TN. Complications include facial numbness and paraesthesia. It remains a useful option in patients not suitable for MVD. TN, like any other chronic pain condition, can have a significant impact on the patient's psychological well-being. Although there is a lack of good quality studies assessing usefulness of psychological interventions, it is worth having a multidisciplinary team including psychologist in managing these patients and considering psychological interventions such as cognitive behavioural therapy and acceptance and commitment therapy.10Fiemann C Newton-John T et al.Psychiatric and psychological management considerations associated with nerve damage and neuropathic trigeminal pain.J Orofac Pain. 2004; 18: 360-365PubMed Google Scholar Neuromodulation techniques targeting the trigeminal nerve, occipital nerves, peripheral nerves, spinal cord, and motor cortex are being performed at some centres, although at present, the evidence is not robust enough to warrant routine use. Non-invasive repetitive transcranial magnetic stimulation of motor cortex has been shown to be of benefit in orofacial pain, including that involving the trigeminal nerve. However, its role in managing TN is yet to be established. There are some case reports and open-ended studies regarding the use of botulinum toxin type A in TN. Well-conducted studies with large samples are required before it can be recommended in TN. Transcutaneous electrical nerve stimulation, acupuncture, and 5% lidocaine patches have also been tried in TN with varying results. Patients with TN suffer one of the most severe pains described. Appropriate and early diagnosis is important to formulate an optimal management plan. Pharmacotherapy with carbamazepine is worth trying in the first instance before considering invasive procedures. As treatment options become more invasive, the results improve, but at the cost of increased side-effects. Hence, it is important to individualize the management plan according to the patient's circumstances.