Trigeminal Neuropathy – Causes, Symptoms, Treatment

Trigeminal Neuropathy/Trigeminal neuralgia (TN), also known as tic douloureux, is the most common neuropathic pain involving the craniofacial region.[rx] It is characterized by sudden, brief, usually unilateral severe recurrent episodes of stabbing pain in the distribution of one or more branches of the trigeminal nerve. Pain is usually described as stabbing, paroxysmal, electric shock-like, or burning pain and is limited to the area innervated by branches of the trigeminal nerve.[rx][rx]

Causes of Trigeminal Neuropathy

The exact cause of trigeminal neuralgia remains unknown.[rx] The majority of cases are referred to as idiopathic, although many are associated with vascular compression of the trigeminal nerve close to its exit from the brainstem by an aberrant loop of an artery or vein. A minority of cases are due to conditions like multiple sclerosis or nerve compression by a tumor.[rx] Some rare causes of trigeminal neuralgia include focal arachnoid thickening, adhesion, traction, tethering or torsion, fibrous ring around the root, cerebellopontine angle tumors, brain stem infarction, aneurysm, and arteriovenous malformation.[rx][rx][rx][rx]

• Vascular Theory – Generally, it has been assumed that vascular contact at the root entry zone causes trigeminal neuralgia; however, TN also may be caused by contact at a transition zone between the central and peripheral myelin. Reportedly, the most common artery involved in this condition is the superior cerebellar artery, as seen in 75% to 80% of TN cases. Persistent primitive trigeminal artery variant, an anomaly that occurs between the carotid and basilar arteries or aneurysms of the persistent primitive trigeminal artery, vertebrobasilar dolichoectasia can cause TN. Sharper trigeminal-pontine angle cisterns and smaller cerebellopontine angle cisterns may facilitate the neurovascular compression (NVC).[rx][rx][rx][rx][rx]
• Extracranial Causes – The most common extracranial cause of trigeminal neuralgia is a perineural spread of head and neck malignancies commonly squamous cell carcinoma, adenoid cystic carcinoma, lymphoma, melanoma, and sarcoma.[rx][rx][rx][rx][rx]
• Classification – TN is classified into idiopathic TN, classic TN, and secondary TN.[rx][rx] Idiopathic TN is characterized by unknown causes and, in approximately 10% of patients, remains without a diagnosed cause, even after surgical procedures or magnetic resonance imaging (MRI). Classic TN is associated with NVC in the trigeminal root entry zone. Secondary TN may be caused by an underlying disease such as tumors, artery malformations, multiple sclerosis.[rx][rx][rx][rx][rx][rx]

Symptoms of Trigeminal Neuropathy 

This disorder is characterized by episodes of severe facial pain along the trigeminal nerve divisions. The trigeminal nerve is a paired cranial nerve that has three major branches: the ophthalmic nerve (V₁), the maxillary nerve (V₂), and the mandibular nerve (V₃). One, two, or all three branches of the nerve may be affected. Trigeminal neuralgia most commonly involves the middle branch (the maxillary nerve or V₂) and lower branch (mandibular nerve or V₃) of the trigeminal nerve.^[rx]

• An individual attack usually lasts from a few seconds to several minutes or hours, but these can repeat for hours with very short intervals between attacks. In other instances, only 4-10 attacks are experienced daily. The episodes of intense pain may occur paroxysmally.
• To describe the pain sensation, people often describe a trigger area on the face so sensitive that touching or even air currents can trigger an episode; however, in many people, the pain is generated spontaneously without any apparent stimulation. It affects lifestyle as it can be triggered by common activities such as eating, talking, shaving, and brushing teeth.
• The wind, chewing, and talking can aggravate the condition in many patients. The attacks are said by those affected to feel like stabbing electric shocks, burning, sharp, pressing, crushing, exploding or shooting pain that becomes intractable.^[rx]
• The pain also tends to occur in cycles with remissions lasting months or even years. 1–6% of cases occur on both sides of the face but extremely rare for both to be affected at the same time. This normally indicates problems with both trigeminal nerves, since one serves strictly the left side of the face and the other serves the right side. Pain attacks are known to worsen in frequency or severity over time, in some people. Pain may migrate to other branches over time but in some people remains very stable.^[rx]
• The rapid spreading of the pain, bilateral involvement or simultaneous participation with other major nerve trunks (such as Painful Tic Convulsif of nerves V & VII or occurrence of symptoms in the V and IX nerves) may suggest a systemic cause. Systemic causes could include multiple sclerosis or expanding cranial tumors.^[rx]
• The severity of the pain makes it difficult to wash the face, shave, and perform good oral hygiene. The pain has a significant impact on activities of daily living especially as people live in fear of when they are going to get their next attack of pain and how severe it will be. It can lead to severe depression and anxiety.^[rx]
• However, not all people will have the symptoms described above and there are variants of TN. One of which is atypical trigeminal neuralgia (“trigeminal neuralgia, type 2” or trigeminal neuralgia with concomitant pain),^[rx] based on a recent classification of facial pain.^[rx] In these instances there is also a more prolonged lower severity background pain that can be present for over 50% of the time and is described more as a burning or prickling, rather than a shock.
• Trigeminal pain can also occur after an attack of herpes zoster, and post-herpetic neuralgia has the same manifestations as in other parts of the body. Trigeminal deafferentation pain (TDP), also termed anesthesia Dolorosa, is from intentional damage to a trigeminal nerve following attempts to surgically fix a nerve problem. This pain is usually constant with a burning sensation and numbness. TDP is very difficult to treat as further surgeries are usually ineffective and possibly detrimental to the person

Diagnosis of Trigeminal Neuropathy

History and Physical

Trigeminal neuralgia causes episodes of spontaneous pain or a triggered intense facial pain limited to one or more divisions of the trigeminal nerve that last for a short duration (a few seconds to two minutes).[rx] Pain may feel like stabbing, electric shocks, burning, pressing, crushing, shooting, migraine-like, piercing, prickling, or a combination of these.[rx] Pain is usually unilateral and rarely bilateral.[rx]

The distribution of TN pain may be in one or more of the territories of the three divisions: ophthalmic (V1), maxillary (V2), and mandibular (V3). V2 is the most frequent territory involved, followed by V3 and then V1.[rx] Pain attacks usually occur by stimulation of trigger points within the territory supplied by the trigeminal nerve. Examples of stimulation include touching the face, tooth brushing, talking, and feeding. A refractory period that can last from a few seconds to several minutes can follow each episode of pain. When attacks are frequent, patients may avoid talking, eating. This can impair the quality of life and mental health in these patients.[rx]

Autonomic symptoms (e.g., mild lacrimation without conjunctival injection) may occur in association with attacks of TN in the V1 trigeminal distribution. This is in clear contrast to the attacks that involve short-lasting unilateral neuralgiform headaches with conjunctival injection, tearing, and rhinorrhea (SUNCT), which are always accompanied by lacrimation and conjunctival injection of the symptomatic side from the onset of symptoms.[rx]

Diagnosis and Criteria

“International Classification of Headache Disorders-3 (ICHD-3) diagnostic criteria.”

• At least three attacks of facial pain, mostly unilateral
• Occurs in one or more divisions of the trigeminal nerve and no radiation beyond the trigeminal distribution

• Pain has all of the following characteristics

  1. Lasts from a fraction of a second to nearly two minutes
  2. Severe intense pain
  3. Electric shock-like, shooting, sharp or stabbing in quality
• Precipitated by innocuous stimuli within the affected trigeminal division
• Not accounted for by another ICHD-3 diagnosis[rx][rx]

Evaluation

The diagnosis of trigeminal neuralgia is mainly clinical. Determining the presence of trigeminal sensory deficits or bilateral involvement of trigeminal nerves should be considered useful to distinguish symptomatic TN from classical TN.[rx]

TN can occur secondary to another disease process such as multiple sclerosis or a cerebellopontine-angle tumor. This is referred to as “symptomatic TN.”[rx]

An MRI detects changes in the trigeminal root, identifies NVC, and may rule out secondary pathology.[rx]

In patients with refractory TN undergoing microvascular decompression (MVD), preoperative high-resolution three-dimensional MRI is a reliable tool in diagnosing NVC.[rx] Imaging consisting of high-resolution three-dimensional fast low angle shot with three-dimensional constructive interference in steady-state can depict the relationship between the intracisternal segment of the trigeminal nerve and the adjacent vessels.[rx]

Lastly, extracranial causes like head and neck malignancies should be considered and evaluated.[rx]

Treatment of Trigeminal Neuropathy

Pharmacologic Therapy

• The first-line treatment for patients with classic TN and idiopathic TN is pharmacologic therapy. The most commonly used medication is the anticonvulsant drug, carbamazepine.[rx] [rx] Carbamazepine or oxcarbazepine should be offered first for pain control.[rx] The usual doses of carbamazepine (200 to 1200 mg/day) and oxcarbazepine (600 to 1800 mg/day) may be administered.[rx] Baclofen, lamotrigine, clonazepam, topiramate, phenytoin, gabapentin, pregabalin, and sodium valproate can be used. When patients cannot take or cannot tolerate high doses of carbamazepine, consider multidrug therapy.[rx] Also, if pain relief is incomplete with carbamazepine, adding a second agent or switching drugs are additional options.[rx][rx]
• Oxcarbazepine is a newer drug and is being increasingly used as first-line therapy for TN in patients who do not respond to or who cannot tolerate carbamazepine. Possible side effects include double vision and dizziness. It can also cause hyponatremia.
• Baclofen is a muscle relaxant that can be used to treat TN. Side effects include dizziness, sedation, and dyspepsia.
• Other medications include lamotrigine, phenytoin, gabapentin, clonazepam, and valproic acid.
• Newer drugs like eslicarbazepine, an active metabolite of oxcarbazepine, and the new Nav1.7 blocker, vixotrigine, are being explored for pain relief in TN.[rx]
• Patients with secondary TN also can respond well to pharmacotherapy. However, it is recommended to treat the underlying lesion or disease.
• Lamotrigine (200 to 400 mg/day), pregabalin (150 to 600 mg/day), gabapentin (1800 to 4200 mg/day), or topiramate (100-400 mg/day) may be considered. If the combination therapy fails, a switch to baclofen (40 to 80 mg/day) may be considered.[rx]
• Intravenous infusion of a combination of magnesium and lidocaine can be very effective in some patients. Botulinum toxin type A injections may be offered before surgery or to those unwilling to undergo surgery and in cases where drug treatments failed. Tetracaine nerve block may be used as an additional treatment after carbamazepine, as well as acupuncture and/or peripheral nerve stimulation.[rx]
• Botulinum Toxin Injections [rx] This can be beneficial for some patients, particularly the middle-aged and the elderly, who are refractory to medical therapy or who cannot tolerate medical therapy due to their side effects.[rx]

Surgical Therapy

• Microvascular decompression [rx]: This is one of the most common procedures used to treat trigeminal neuralgia. This is beneficial for patients with TN, where compression of the nerve root is the cause. This involves craniotomy and posterior fossa exploration for identifying and moving the blood vessel that is compressing the trigeminal nerve. A soft cushion is then inserted between the nerve and the vessel, to allow the nerve to recover, which eventually relieves the pain. In some patients, this procedure can result in sustained pain relief for greater than 10 years. Though this is the most effective procedure, it is also the most invasive one. Some of the complications associated with it are decreased hearing, cerebellar hematoma, CSF leaks, infarction, and facial weakness. It is believed to be the most effective long term surgical treatment available currently for patients with TN.[rx]
• Ablative procedures include rhizotomy – with thermocoagulation, chemical injection, or mechanical balloon compression. These procedures involve damaging the trigeminal nerve root, thereby interrupting the pain transmission signals to the brain. Rhizotomy with thermocoagulation uses an electrode to apply heat to damage the nerve fibers. Chemical rhizotomy involves injecting the chemical, glycerol to the trigeminal nerve, thereby damaging it. Balloon compression involves inserting a tiny balloon to the point of location of nerve fibers.[rx][rx] This balloon, on inflation, damages the nerve fibers. Some of the associated complications are postoperative dysesthesia, corneal numbness, sensory loss in trigeminal nerve distribution, and anesthesia dolorosa.
• Radiosurgery – This procedure involves using radiosurgery instrumentation.[rx][rx][rx] This is a non-invasive procedure, wherein, a highly concentrated dose of ionizing radiation is delivered to a precise target at the trigeminal nerve root. The radiation creates a lesion near the nerve root, thereby interrupting the pain signals from transmission to the brain. The formation of the lesion can be slow, and hence the pain relief using this procedure is delayed by up to several weeks or months. As this is one of the least invasive procedures, it can be repeated in patients who have a recurrence of pain. Some of the associated complications can be facial sensory loss and paresthesias.
• Peripheral neurectomy and nerve block – The neurectomy can be performed on peripheral branches of trigeminal nerve like the supraorbital, infraorbital, lingual, and alveolar nerves.[rx] This can be accomplished by alcohol injection, incision, cryotherapy, or radiofrequency lesioning. Peripheral neurectomy can be safe in elderly patients in remote and rural areas, where neurosurgical facilities are not readily available.[rx] However, the evidence regarding these peripheral techniques for trigeminal neuralgia is inconclusive.

Complications

• The pain in trigeminal neuralgia is so severe and debilitating that the patients can develop depression, if not adequately treated.
• Patients with severe pain associated with facial twitches can become socially withdrawn due to embarrassment and fear of an impending attack.
• Patients treated with anticonvulsant drugs over the long term can have adverse drug effects.
• Microvascular decompression and percutaneous neurosurgical procedures can pose surgical risks.
• Some patients permanently develop facial numbness on the affected side.
• Occasionally, patients develop corneal anesthesia and jaw weakness.
• Anesthesia dolorosa is seen in a few patients. It is an intractable facial dysesthesia, which can be more disabling than original TN.