Hyponatremia-induced worsening of trigeminal neuralgia- When the sodium plays the game

ABSTRACT

A 78-year-old elderly male who was on treatment for trigeminal neuralgia and hypertension was brought to the emergency with altered sensorium. His vital parameters were within normal limits; however, the arterial blood gas analysis showed severe hyponatremia. He was admitted to the ward, where further workup was carried out and hyponatremia correction started. He had a sudden worsening in his facial pain before he landed in encephalopathy. His medications (oxcarbazepine and chlorthalidone) that could cause hyponatremia were stopped, and judicious correction of hyponatremia was done. His baseline investigations, including a chest roentgenogram and electrocardiogram, were normal. After he regained consciousness, it was noted that the facial pain had regressed significantly despite stopping his first-line drugs. This case of worsening trigeminal neuralgic pain due to hyponatremia responded well to judicious sodium correction.

Introduction

Trigeminal neuralgia (TN) is a condition characterized by sudden, mostly unilateral, short-lasting, stabbing, recurrent pain with a distribution consistent with one or more divisions of the fifth cranial nerve.[1] The pain can have various triggers such as talking, shaving, jaw movements, or even a light touch or breeze.[2] Hyponatremia, which is the most common electrolyte abnormality encountered in day-to-day clinical practice, is defined as serum sodium levels below 135 mEq/L. There can be different types of hyponatremias: 1) hypervolemic hyponatremia, 2) euvolemic hyponatremia, and 3) hypovolemic hyponatremia. It may be seen in isolation or combined with other electrolyte disturbances. It can be acute or chronic and may vary from being totally asymptomatic to an extremely critical condition. There are many diseases (e.g. heart failure, renal failure, and fluid loss) and drugs (e.g. diuretics, antipsychotics, and antidepressants) that may cause hyponatremia. There can be a syndrome of inappropriate antidiuretic hormone secretion (SIADH) that can be caused by multiple factors, including certain drugs. Oxcarbazepine is one of them, which can cause hyponatremia of different degrees with a prevalence of 23%–73%.[3,4] The principal extracellular cation is sodium, and the principal intracellular cation is potassium, and together with other electrolytes and channels, a constant osmotic gradient is maintained across the neurons. This osmotic gradient can affect neuronal physiology.[5] It is also supported by studies showing changes in nerve conduction studies and F-wave latencies in hyponatremia.[6,7] To the best of our knowledge and after an exhaustive review of the literature, it is noted that worsening of trigeminal neuralgic pain due to hyponatremia has not been reported before. Our patient improved significantly within 72 h of correction in sodium levels. Hyponatremia may hinder action potential generation and hence lead to paraesthesia.

Case Report

A 78-year-old male was admitted with altered sensorium, hiccups, and vomiting with a Glasgow Coma Scale level of 7 out of 15. His blood pressure, pulse rate, and respiratory rate, including oxygen saturation, were normal. He was a known case of trigeminal neuralgia diagnosed 6 months ago and was on tablets of oxcarbazepine (300 mg twice daily) and amitriptyline (12.5 mg once daily). He had been hypertensive for 6 years and was on tablets of Nifedipine Retard 10 mg twice daily and Chlorthalidone 6.25 mg once daily. His chest X-ray was normal. An electrocardiogram showed normal sinus rhythm. Non-contrast computed tomography of the head was done, which revealed cerebral atrophy with no other features. A magnetic resonance imaging (MRI) of the brain with intracranial angiography [Figures 1 and 2] was normal. On admission, he was euvolemic with sodium levels of 112 mEq/L. The patient was started on a 3% saline infusion at a rate of 15 mL/h. Drugs that could cause hyponatremia (chlorthalidone, amitriptyline, and oxcarbazepine) were stopped. His sensorium started to improve within 6 h of initiating hypertonic saline. After 12 h, he was conscious and oriented. He was started on semisolid food, but he could not take it as he had severe facial and jaw pain. On questioning about the duration of pain and its intensity, he could say that it was mild (numeric pain rating scale = 2–3) until 7 days before it became severe (numeric pain rating scale = 8–9) and excruciating. A dentist’s opinion was sought, but there was no significant local abnormality noted. On day 2, his repeat serum sodium was 124 mEq/L, and hence hypertonic saline was stopped, and oral salt was added for further correction. His complete hemogram, liver function test, serum creatinine, and urine routine were within normal levels. His serum osmolality and spot urine sodium were 237 mOsm/kg and 40 mEq/L, respectively; however, his urine osmolality was not checked. He had normal values of serum cortisol (morning sample: 21.58) and TSH (4.5 IU/mL). As he was on diuretics for hypertension, investigations in the line of SIADH were skipped. The neurologist’s opinion was taken, and the patient was started on Gabapentin 300 mg thrice daily, which further relieved his facial pain. On day 4, his facial pain was significantly relieved, and serum sodium came up to 137 mEq/L; so, he was discharged. Follow-up thereafter did not show a fall in serum sodium level, and he is doing well.

Figure 1.

Normal MRI brain

Figure 2.

Normal intracranial angiography

Discussion

Hyponatremia is the most common electrolyte imbalance seen in patients globally. Patients with hyponatremia can present with varying degrees of manifestation, from asymptomatic to throwing seizures and landing in a catastrophic state such as altered sensorium and even coma. It is not uncommon to see hyponatremia in patients with trigeminal neuralgia, which can be caused by drugs used for symptomatic relief. Had our patient not lapsed into a state of altered sensorium that led to his diagnosis of severe hyponatremia, there would have been an increase in the doses of oxcarbazepine and amitriptyline or the addition of new drugs as he had worsening facial pain. Though there are mechanisms that explain the pain in trigeminal neuralgia, such as demyelination and a dysregulation of voltage-gated sodium channel expression, there are no known facts or studies that well explain the worsening of neuralgic pain due to hyponatremia.[8,9] Although in a patient with severe hyponatremia, cerebral edema occurs due to the involvement of astrocytes (constituents of the blood–brain barrier) that swell up in response to a change in the osmotic gradient, there is sparing of neurons.[10] In another study, hyponatremia-related osmotic edema was also associated with the activation of N-methyl-d-aspartate receptors and increased neuronal excitability.[11] There can be generalized paraesthesia and localized neuropathic pain in hyponatremia. Menchaca K. et al. reported a case where glossopharyngeal neuralgia was caused by severe hyponatremia in a patient with COVID-19 infection.[12] Similarly, there are other reports of hyponatremia with pain, but the pain was either in the abdomen or lower limbs secondary to disseminated encephalomyelitis but not trigeminal neuralgia.[13,14] Sometimes, pain is noted with hyponatremia, but the definite etiology of pain may be different, like in the case of a 20-year-old girl, where it was found to be due to acute intermittent porphyria.[15] There are some studies where pain signaling has been associated with voltage-gated sodium channels.[16] Our patient had isolated pain in the fifth cranial nerve distribution that regressed with improvement in the serum sodium levels, which makes us think of the role of hyponatremia in the worsening of trigeminal neuralgic pain.

Conclusion

All patients who are on medications for trigeminal neuralgia need to be advised to have serum electrolyte monitoring on a regular basis. Even if there is a worsening of neuralgic pain, electrolytes may be checked before going for an increase in the drug dose or the addition of a new drug. Though this case throws some light on the possible cause of a sudden worsening in facial pain, large-scale studies are required to be sure of the connection between serum sodium and neuralgic pain.

Declaration of patient consent

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Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.