Introduction

Mumps is a highly infectious disease caused by the mumps virus, a member of the Paramyxoviridae family of enveloped, non-segmented, negative-sense RNA viruses. While in most conditions, the mumps infections are mild and self-limiting However, they can lead to severe complications. The most predominant signs and symptoms start with inflammation of parotitis and orchitis. Among the complications caused by mumps, the most concerning areas are the central nervous system (CNS) due to their serious and lasting impacts on human life. They are meningitis, encephalitis, and sensorineural hearing loss. The mumps virus is highly neurotropic, with laboratory evidence of central nervous system (CNS) infection in approximately half of cases. A crucial ways to develop preventive strategies is better understanding of the complications by diseases especially when we work up from the public health point of view. Understanding the neurological complications associated with the disease is crucial to develop preventive strategies in the field of public health. Even in this modern tech world, despite the availability of vaccines, outbreaks are still occurring, not only in underdeveloped countries or low vaccine coverage countries but also in the developed West. This article aims to provide a comprehensive understanding of mumps, especially neurological complications, epidemiology, pathophysiology, diagnostics and management options, and prevention strategies.

History of mumps 

The first description of the mump virus was done by the Hippocrates in the fifth century bc, in his first Book of Epidemics, but the aetiology was not demonstrated until the 1930s and it was done by Johnson and Goodpasture from the infected rhesus macaques (Macaca mulatta).¹ The prime targets are the children aged between 5 and 9 years. 

In recent years, there has been a shift in the increasing number of cases occurring in adolescents and young adults. This paradigm shift is largely due to waning immunity from the vaccine over time and the higher mobility and close-contact settings in these age groups. The mumps are categorised as a notifiable disease in England and Wales.

Mumps vaccines (live attenuated) have been available since the 1960s. Most European countries have had routine childhood mumps immunisation since the 1980s. With the advent of the Measles, Mumps, and Rubella (MMR) vaccine, the incidence rates of the mumps have been significantly decreased in many parts of the world. Of all the advancements, the disease has not been eradicated, and outbreaks still occur, mostly in the low vaccination coverage areas.

Stages and Symptoms

Early acute stage: Virus progression

• Headache
• Malaise
• Myalgia
• Fever

Advanced stage: Viruria

• Parotitis
• Orchitis
• Pancreatitis
• Meningitis
• Encephalitis
• Deafness

Transmission

The mumps virus transmits through the respiratory route by inhalation of oral droplets with infected secretions. The virus initially infects the upper respiratory epithelium, following initial replication in these cells, the virus spreads to regional lymph nodes, leading to primary viremia during the early acute phase. The primary viremia stage is followed by the virus attacking various tissues in the body, leading to secondary viremia, particularly starts with the parotid glands. The virus infects the glandular epithelial cells, then follows inflammation, necrosis and swelling. Approximately one-third to one-half of infections are asymptomatic or result in only mild respiratory symptoms, sometimes accompanied by fever. 

Parotitis, orchitis and other manifestations 

The main hallmark sign of mumps is the painful swelling of salivary glands, typically the parotid glands, which form the basis of a clinical diagnosis. The swelling develops 2-3 weeks after the exposure, and lasts for 2-3 days and sometimes may persist for a week or more.^2,3 Other areas like submaxillary, submandibular, and sublingual glands can also be involved. The virus is excreted in the saliva from approximately 1 week before to after the onset of salivary gland swelling.^4,5 

. The most common extra-salivary gland manifestation is orchitis, occurring approximately in 10-20 % of infections in postpubertal men.⁶,⁷ The orchitis is always accompanied by epididymitis and fever, which may resolve in a week. The mumps virus frequently disseminates into the kidneys followed by the viruria during the acute phase of the disease. It can cross the blood-brain barrier and infect the central nervous system. The viral invasion through infected mononuclear cells or the olfactory bulb, or via hematogenous spread, causes mumps meningitis or mumps encephalitis. The host's immune response to the virus involves both humoral and cellular immunity. The virus spread is controlled by neutralising the antibodies targeting the HN and F glycoproteins, in which cytotoxic T cells play a major role. However, the immune response also contributes to tissue damage and inflammation seen in various organs, including the CNS.

Neurological complications

The most common neurological complications of mumps virus are as follows:

• Aseptic meningitis
• Acute encephalitis
• Chronic encephalitis
• Hydrocephalus
• Ataxia
• Transverse myelitis
• Guillain-Barré syndrome
• Deafness.

Among these complications, acute and chronic encephalitis, hydrocephalus, transverse myelitis and deafness occasionally result in severe sequelae. Aseptic meningitis due to mumps vaccine strain increased significantly after the introduction of trivalent measles, mumps and rubella vaccinations.⁸

Meningitis and encephalitis

The mumps virus is highly neurotropic, with evidence of central nervous system (CNS) involvement in up to half of all cases of infection. It infects the central nervous system and is based on pleocytosis of the cerebrospinal fluid.^{9, 10} In the CNS, the virus causes inflammation of the meninges (mumps meningitis) or brain parenchyma (mumps encephalitis). Meningitis occurs in approximately 5-10 % cases and encephalitis in less than 0.5 % cases. Symptoms include headache, neck stiffness, photophobia, and fever. Some rare cases of encephalitis the patients have altered mental status, seizures, focal neurological deficits, and sometimes coma. In unvaccinated populations, mumps continues to account for a high percentage of viral encephalitis cases.¹¹ Since the disease is fatal, little is known of the CNS pathology. However, the virus can be recovered from cerebrospinal fluid in the early course of meningitis as well as from brain tissue in some mumps encephalitis cases.¹² The animal data models reveal that the virus once the enters the CSF, is carried throughout the ventricular system, resulting in replication within ependymal cells. Then the virus can penetrate through the brain parenchyma, infecting cerebral cortex and hippocampus13,14The infected epithelium becomes inflamed, degenerated and collapses into cerebrospinal fluid, which is responsible for the hydrocephalus. The findings in humans suggest that the ependymal cell debris in the cerebrospinal fluid of mumps patients is similar to the mechanism of hydrocephalus in animal models.

Diagnosis

Elevated white blood cell counts in the cerebrospinal fluid, through lumbar puncture is on the diagnostic methodology. PCR testing can detect mumps RNA in the CSF, confirming viral aetiology.

Treatment 

There is no specific antiviral treatment for mumps meningitis and encephalitis; most of the cases require support, including analgesics for pain and antipyretics for fever. Management of seizures and monitoring for increased intracranial pressure plays a vital role in care. The mumps meningitis is self-limiting and resolves without long-term sequelae. Hospitalisation may be required for severe cases. The prognosis varies; while many patients recover fully, some may experience long-term neurological deficits, such as cognitive impairment or motor dysfunction.

Sensorineural hearing loss

The mumps virus can also affect the auditory system, leading to unilateral or bilateral sensorineural hearing loss. This occurs due to viral-induced damage to the cochlea or the auditory nerve. Nearly 4 % of mumps cases reported deafness and it is the most frequent cause of acquired unilateral sensorineural hearing loss in children. The hearing loss is unilateral but can be permanent.¹⁵,¹⁶ Some studies suggest that the deafness does not occur more frequently in patients with meningitis or encephalitis than it does in patients lacking signs of central nervous system infection, suggesting that cerebrospinal fluid may in fact not be involved in the pathogenesis of deafness. Other alternative route, the virus infects the inner ear via a haematogenous route, that is mumps labyrinthitis occurs as a consequence of viraemia, which were supported by studies in guinea pigs following intravascular inoculation of the virus, and clinical findings by Lindsay, and Mizushima and Murakami suggesting 'viral endolymphatic labyrinthitis' in the pathogenesis of deafness in mumps infected humans.^17,18,19

Hearing loss from mumps can be transient or permanent. Unilateral hearing loss is common, but bilateral hearing loss may also occur. Early detection is crucial for effective management, the usual diagnosis of hearing loss is through audiometric testing. The steroid drugs can reduce the inflammation, but their efficiency is not well established. Other options include hearing aids and cochlear implants for those with severe loss.

Prevention and public health implications

Vaccine

The Measles, Mumps, and Rubella (MMR) vaccine is one of the important discoveries, centres on mumps prevention, providing approximately 88% effectiveness against mumps. The vaccine can be administered in two doses, first dose at 12-15 months of age and the second at 4-6 years of age. One of the ways to control outbreak and break is advancing the high vaccination coverage which is essential for maintaining herd immunity, we may reduce the incidence of mumps and its complications.

Public health strategies

Public health campaigns by educating the public about the importance of vaccination and surveillance systems are crucial for reducing the risk of virus outbreak early. The vaccination and isolation protocols for infected individuals can help in controlling the spread of the virus. Global health organisations also work to ensure access to vaccines worldwide. Global cooperation is essential to control mumps internationally, more focus has to be in vaccine drives especially in the low-income countries. Proper understanding of the clinical features, manifestation are important for prevention and in building treatment strategies. Continued research is needed to better understand the mechanisms of CNS invasion and the long-term impacts of neurological complications, even though the availability of the MMR vaccine.

FAQ’s

What are the severe complications of mumps?

Oophoritis, mastitis, pancreatitis, encephalitis, meningitis are the severe complications in advanced stages. 

Is the mumps serious?

Yes, in the advanced stages it can cause meningitis, encephalitis which may be fatal. 

What are the chances of surviving mumps?

Fatality rate of mumps is 1.6-3.8 people per 10,000.