Measles Induced Encephalitis

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2	format correction	Dean Liu	Meta information modification	1281	2022-11-28 04:20:32	\|

This entry is adapted from the peer-reviewed paper 10.3390/diseases10040104

Encephalitis, a well-known complication of measles, is inflammation of the brain parenchyma which is mostly due to the viral invasion of neurons. It presents with a variety of symptoms ranging from mild to severe depending on the extent of the damaged neurons.

encephalitis measles COVID-19 prevention

1. Introduction

The measles virus, a single-stranded RNA virus, belongs to the paramyxovirus family and is well-known throughout the world for causing measles. In some individuals, it may eventually lead to the development of a variety of complications, some of which could be fatal. In recent years, measles infection has become of prime concern due to the fact that despite the wide availability of effective vaccines against the virus, a sudden upsurge in cases of measles was noted by the World Health Organization (WHO) towards the end of 2019 in states of America with a previously recognized eradication of the virus ^[1]^[2]. From the experts’ points of view, the negligence regarding administration of the measles vaccine observed during the recent coronavirus disease (COVID-19) outbreak might be one of the causative factors along with the declining effectiveness of the measles vaccine ^[1]. The US Centers for Disease Control and Prevention (CDC) reported 16 new cases of measles in September 2021, most of which were found in Afghan refugees and US citizens ^[3]. In October 2021, Nigeria, Pakistan, Somalia, and India topped the list of countries reporting the highest number of measles cases ^[2]. Since the emergence of COVID-19, there have been drastic shifts in interest of researchers, scientists, news reporters, and various non-government organizations (NGOs) from already prevalent infectious diseases to the sudden eruption of this novel and peculiar COVID-19 virus and its associated lethality. The virus attracted all the attention and thereby lifted necessary focus from other infective agents, leading to the postponement of previously scheduled vaccination campaigns for measles ^[2]^[4]. To date, measles remains the most contagious disease around the world, with an R0 (basic reproduction number) ranking of 12–18, meaning an infected person is likely to spread the disease to an average of 12–18 people (in a totally susceptible population). The high contraction rate of measles poses a major threat to scientists to come up with efficient methods for wisely tackling the outbreak ^[5].

2. Pathogenesis

The measles virus, acquired via aerosol droplets, has an increased propensity for invading the dendritic and alveolar macrophages of the host’s respiratory tract ^[6]. The process is initiated and fueled by the presence of signaling lymphocytic activation molecule (CDw150) and Nectin-4 on human immune cells and epithelial cells respectively, allowing efficient interaction with the virus ^[6]. This interaction between the receptors and the virus is crucial for permitting entry of the virus into the cell. Once the invasion is complete, the virus may further proceed to enter other organs through the bloodstream and start replicating in the lymphocytes. Evidence from multiple research studies signify that the virus is highly capable of causing major disruptions to the host’s immune mechanisms, which can render the person increasingly susceptible to opportunistic infections along with the decreased capacity to fight them. This immunomodulation includes decreased functional capacity and count of CD4+ and CD8+ T lymphocytes and reduced production of Interleukin-12 (IL-12), which is responsible for initiating T-helper 1 responses ^[7].

3. Signs and Symptoms

The incubation period, which refers to the time from exposure to the onset of the first symptom, is approximately 11 to 12 days in measles with fever, cough, coryza, Koplik spots and measles rash being the most common presentations ^[8]. Koplik spots are blue-white spots that usually appear before the morbilliform rash on the buccal mucosa. The measles rash is characterized by a maculopapular eruption beginning from the neck, involving the face and later adopting a centrifugal spread pattern to involve upper and lower extremities as well as the trunk ^[8]. The infectivity period of measles, which is the duration with the highest chance of the transmission of the infective agent, is 4 days before the onset of rash and 4 days after the rash ^[8]. Though the primary measles infection usually presents with pyrexia, coryza and maculopapular rash, the alarm bells ring when an individual infected with measles starts developing neurological symptoms secondary to viral invasion of the neurons. Neurological and respiratory complications have proved to be important and the most common causes of death from measles ^[9]. These complications were more commonly observed in children younger than 5 years and adults, as well as a few immunocompromised or debilitated individuals ^[8]. Diarrhea and otitis media are other two well-recognized complications of measles ^[10].

4. Encephalitis and Its Types

Encephalitis, which is the inflammation of the brain parenchyma, is a rare but devastating complication of measles, denoting that the virus has breached the neuronal membrane or, undergoing a possible epitope matching phenomenon, the virus might have triggered an inflammatory response in the host. Measles-induced encephalitis has four distinct presentations requiring different approaches. Encephalitis may either follow an acute course (primary measles encephalitis and acute encephalitis) or have a chronic presentation. Chronic presentation is further subdivided into measles inclusion body encephalitis and subacute sclerosing panencephalitis (SSPE) ^[11].

Primary measles encephalitis occurs during the ongoing primary measles infection and is likely to present in the first week along with the appearance of the characteristic measles rash ^[12]. The probability of infected people eventually developing primary measles encephalitis is 1 in 1000, and the associated mortality rate is 10–15% ^[13]. It is highly likely to be caused by the virus directly invading the neuronal cells ^[12].

Acute encephalitis due to measles, also known as ‘post-infectious encephalitis’, is coupled with a 20% mortality rate and may manifest with fever, headaches, altered sensorium, and even later development of debilitating neurological deficit ^[11]. Some studies suggest that the activation of the autoimmune mechanism may be the causative factor, whereas other studies favor direct viral invasion to be the prime cause of encephalitis ^[14]. Due to the scarcity and reliability of available data, it is hard to state the exact pathogenesis of acute encephalitis.

The third type of measles inclusion body encephalitis (MIBE) also known as subacute measles encephalitis, is more likely to be observed in people with compromised immunity, and the presentation may progress from an initial altered level of consciousness to worsening seizures, eventually leading to established epilepsy and focal neurological deficits such as aphasia (inability to talk), hemiplegia (paralysis of one side of the body), and ataxia (lack of coordination of movements) ^[12]^[15]. The mortality rate ascribed to MIBE is 75% ^[12].

Subacute sclerosing panencephalitis, a chronic demyelinating disease, is a result of persistent viral invasion of the neurons, reactivation of previously acquired measles virus, or an underdeveloped immune system as seen in children younger than 2 years of age ^[12]^[16]. Recent molecular studies suggest viral F-protein to be responsible for neurovirulence by undergoing conformational change from a perfusion state to a steadier post-fusion state, thereby promoting healthy viral and host cell interactions ^[17]. Histopathology of the disease suggests the involvement of oligodendrocytes, astrocytes and endothelial cells showing the presence of inclusion bodies and/or fibrillary tangles ^[16]. The infective course begins with typical cellular swelling along with nuclear degeneration induced by oxidative stress, and later progresses to demyelination of the neurons ^[18]. Leukocytes infiltrating the brain parenchyma indicate the presence of an ongoing acute inflammatory response which later exhibits symptoms with respect to the extent of damage that has been done. The symptoms begin with certain behavioral changes and decreased efficiency, and progress toward subsequent cognitive decline and significant motor deficits which can later prove to be fatal. Clinical changes observed in the diagnosis of SSPE are divided into four stages. Changes seen in stage one include behavioral and cognitive decline. Myoclonic jerks, seizures, and dementia are likely to be seen in stage two. Stage three presents with rigidity, extrapyramidal symptoms, and progressive unresponsiveness. Stage four is the last stage and involves coma, persistent vegetative stage, akinetic mutism, and autonomic instability ^[19]. The mortality rate is around 95% ^[18].

References

Worldwide Measles Cases Climb. Outbreak Observatory. Available online: https://www.outbreakobservatory.org/outbreakthursday-1/3/11/2021/worldwide-measles-cases-climb (accessed on 17 January 2022).
Measles Outbreaks May Dominate 2022. Available online: https://www.precisionvaccinations.com/measles-outbreaks-may-dominate-2022 (accessed on 17 January 2022).
News Scan for Sep 21, 2021. CIDRAP. Available online: https://www.cidrap.umn.edu/news-perspective/2021/09/news-scan-sep-21-2021 (accessed on 17 January 2022).
Global Progress against Measles Threatened Amidst COVID-19 Pandemic. Available online: https://www.who.int/news/item/10-11-2021-global-progress-against-measles-threatened-amidst-covid-19-pandemic (accessed on 17 January 2022).
Guerra, F.M.; Bolotin, S.; Lim, G.; Heffernan, J.; Deeks, S.L.; Li, Y.; Crowcroft, N.S. The basic reproduction number of measles: A systematic review. Lancet Infect. Dis. 2017, 17, e420–e428.
Noyce, R.S.; Bondre, D.G.; Ha, M.N.; Lin, L.T.; Sisson, G.; Tsao, M.S.; Richardson, C.D. Tumor Cell Marker PVRL4 Is an Epithelial Cell Receptor for Measles Virus. PLoS Pathog. 2011, 7, e1002240.
Moss, W.J.; Griffin, D.E.; Feinstone, W.H. Measles. Vaccines Biodef. Emerg. Negl. Dis. 2009, 551–565.
Pinkbook: Measles|CDC. 2021. Available online: https://www.cdc.gov/vaccines/pubs/pinkbook/meas.html (accessed on 17 January 2022).
Barkin, R.M. Measles Mortality: Analysis of the Primary Cause of Death. Am. J. Dis. Child. 1975, 129, 307.
Measles Complications|CDC. Available online: https://www.cdc.gov/measles/symptoms/complications.html (accessed on 17 January 2022).
Ferren, M.; Horvat, B.; Mathieu, C. Measles Encephalitis: Towards New Therapeutics. Viruses 2019, 11, 1017.
Fisher, D.L.; Defres, S.; Solomon, T. Measles-induced encephalitis. QJM 2015, 108, 177–182.
Primary Measles Encephalitis. J. Educ. Teach. Emerg. Med. 21 March 2020. Available online: https://jetem.org/measles_sim/ (accessed on 17 January 2022).
Hosoya—2006—Measles Encephalitis Direct Viral Invasion or Aut.pdf. Available online: https://www.jstage.jst.go.jp/article/internalmedicine/45/14/45_14_841/_pdf/-char/en (accessed on 17 January 2022).
Chakraborty, A.P.; Ray, A.; Mukherjee, D.; Gupta, S.; Pandit, A.; Dubey, S. Subacute measles encephalitis in a case of late presenting congenital HIV with epilepsia partialis continua as the first manifestation: A case report. J. Fam. Med. Prim Care 2021, 10, 3502–3504.
Pathogenesis of Encephalitis Caused by Persistent Measles Virus Infection|IntechOpen. Available online: https://www.intechopen.com/chapters/41738 (accessed on 17 January 2022).
jgv001682.pdf. Available online: https://www.microbiologyresearch.org/docserver/fulltext/jgv/102/10/jgv001682.pdf?expires=1642446499&id=id&accname=guest&checksum=A6CC91060D2248BABE93C3CE42A5075E (accessed on 17 January 2022).
Rocke, Z.; Belyayeva, M. Subacute Sclerosing Panencephalitis. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. Available online: http://www.ncbi.nlm.nih.gov/books/NBK560673/ (accessed on 17 January 2022).
Jafri, S.K.; Kumar, R.; Ibrahim, S.H. Subacute sclerosing panencephalitis—Current perspectives. Pediatr. Health Med. Ther. 2018, 9, 67–71.

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Domenico De Berardis

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Entry Collection: Neurodegeneration

Update Date: 28 Nov 2022

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