Viral meningitis

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Viral meningitis
Other namesAseptic meningitis
Meninges-en.svg
Viral meningitis causes inflammation of the meninges.
Specialty Neurology

Viral meningitis, also known as aseptic meningitis, is a type of meningitis due to a viral infection. It results in inflammation of the meninges (the membranes covering the brain and spinal cord). Symptoms commonly include headache, fever, sensitivity to light and neck stiffness. [1]

Contents

Viruses are the most common cause of aseptic meningitis.[ medical citation needed ] Most cases of viral meningitis are caused by enteroviruses (common stomach viruses). [2] [1] [3] However, other viruses can also cause viral meningitis, such as West Nile virus, mumps, measles, herpes simplex types I and II, varicella and lymphocytic choriomeningitis (LCM) virus. [1] [4] Based on clinical symptoms, viral meningitis cannot be reliably differentiated from bacterial meningitis, [5] although viral meningitis typically follows a more benign clinical course. Viral meningitis has no evidence of bacteria present in cerebral spinal fluid (CSF). Therefore, lumbar puncture with CSF analysis is often needed to identify the disease. [6]

In most cases, there is no specific treatment, with efforts generally aimed at relieving symptoms (headache, fever or nausea). [7] A few viral causes, such as HSV, have specific treatments.

In the United States, viral meningitis is the cause of more than half of all cases of meningitis. [8] [9] With the prevalence of bacterial meningitis in decline, the viral disease is garnering more and more attention. [10] The estimated incidence has a considerable range, from 0.26 to 17 cases per 100,000 people. For enteroviral meningitis, the most common cause of viral meningitis, there are up to 75,000 cases annually in the United States alone. [10] While the disease can occur in both children and adults, it is more common in children. [1]

Signs and symptoms

Symptoms of Meningitis Symptoms of Meningitis.png
Symptoms of Meningitis

Viral meningitis characteristically presents with fever, headache and neck stiffness. [11] Fever is the result of cytokines released that affect the thermoregulatory (temperature control) neurons of the hypothalamus. Cytokines and increased intracranial pressure stimulate nociceptors in the brain that lead to headaches. Neck stiffness is the result of inflamed meninges stretching due to flexion of the spine. [12] The various layers of meninges act form a separation between the brain and the skull. [13] In contrast to bacterial meningitis, symptoms associated with viral meningitis are often less severe and do not progress as quickly. [11] Nausea, vomiting and photophobia (light sensitivity) also commonly occur, as do general signs of a viral infection, such as muscle aches and malaise. [11] Increased cranial pressure from viral meningitis stimulates the area postrema, which causes nausea and vomiting. Widened pulse pressure (systolic - diastolic blood pressure), bradycardia, and irregular respiration would be alarming for Cushing's reflex, a sign of acutely elevated intracranial pressure. [14] Photophobia is due to meningeal irritation. [12] In severe cases, people may experience concomitant encephalitis (meningoencephalitis), which is suggested by symptoms such as altered mental status, seizures or focal neurologic deficits. [15]

Babies with viral meningitis may only appear irritable, sleepy or have trouble eating. [6] Infection in the neonatal period may be the result of infection during pregnancy. [1] In severe cases, people may experience concomitant encephalitis (meningoencephalitis), which is suggested by symptoms such as altered mental status, seizures or focal neurologic deficits. [15] The pediatric population may show some additional signs and symptoms that include jaundice and bulging fontanelles. [12] A biphasic fever is more often seen in children compared to adults. The first fever arrives with the onset of general constitutional symptoms, and the second accompanying the onset of the neurological symptoms. [16]

Symptoms can vary depending on the virus responsible for infection. Enteroviral meningitis (the most common cause) typically presents with the classic headache, photophobia, fever, nausea, vomiting, and nuchal rigidity. [17] With coxsackie and echo virus' specifically, a maculopapular rash may be present, or even the typical vesicles seen with Herpangina. [17] Lymphocytic choriomeningitis virus (LCMV) can be differentiated from the common presenting meningeal symptoms by the appearance of a prodromal influenza-like sickness about 10 days before other symptoms begin. [17] Mumps meningitis can present similarly to isolated mumps, with possible parotid and testicular swelling. [17] Interestingly, research has shown that HSV-2 meningitis most often occurs in people with no history of genital herpes, and that a severe frontal headache is among the most common presenting symptoms. [18] [17] Patients with varicella zoster meningitis may present with herpes zoster (Shingles) in conjunction with classic meningeal signs. [17] Meningitis can be an indication that an individual with HIV is undergoing seroconversion, the time when the human body is forming antibodies in response to the virus. [1]

Causes

The most common causes of viral meningitis in the United States are non-polio enteroviruses. The viruses that cause meningitis are typically acquired from sick contacts. However, in most cases, people infected with viruses that may cause meningitis do not actually develop meningitis. [6]

Viruses that can cause meningitis include: [19]

Mechanism

Meningitis

Viral Meningitis is mostly caused by an infectious agent that has colonized somewhere in its host. [20] People who are already in an immunocompromised state are at the highest risk of pathogen entry. [12] Some of the most common examples of immunocompromised individuals include those with HIV, cancer, diabetes, malnutrition, certain genetic disorders, and patients on chemotherapy. [12] Potential sites for this include the skin, respiratory tract, gastrointestinal tract, nasopharynx, and genitourinary tract. The organism invades the submucosa at these sites by invading host defenses, such as local immunity, physical barriers, and phagocytes or macrophages. [20] After pathogen invasion, the immune system is activated. [12] An infectious agent can enter the central nervous system and cause meningeal disease via invading the bloodstream, a retrograde neuronal pathway, or by direct contiguous spread. [21] Immune cells and damaged endothelial cells release matrix metalloproteinases (MMPs), cytokines, and nitric oxide. MMPs and NO induce vasodilation in the cerebral vasculature. Cytokines induce capillary wall changes in the blood brain barrier, which leads to expression of more leukocyte receptors, thus increasing white blood cell binding and extravasation. [12]

The barrier that the meninges create between the brain and the bloodstream are what normally protect the brain from the body's immune system. Damage to the meninges and endothelial cells increases cytotoxic reactive oxygen species production, which damages pathogens as well as nearby cells. [12] In meningitis, the barrier is disrupted, so once viruses have entered the brain, they are isolated from the immune system and can spread. [22] This leads to elevated intracranial pressure, cerebral edema, meningeal irritation, and neuronal death. [12]

Diagnosis

Lumbar Puncture Blausen 0617 LumbarPuncture.png
Lumbar Puncture

The diagnosis of viral meningitis is made by clinical history, physical exam, and several diagnostic tests. [23] Kernig and Brudzinski signs may be elucidated with specific physical exam maneuvers, and can help diagnose meningitis at the bedside. [17] Most importantly however, cerebrospinal fluid (CSF) is collected via lumbar puncture (also known as spinal tap). This fluid, which normally surrounds the brain and spinal cord, is then analyzed for signs of infection. [24] CSF findings that suggest a viral cause of meningitis include an elevated white blood cell count (usually 10-100 cells/µL) with a lymphocytic predominance in combination with a normal glucose level. [25] Increasingly, cerebrospinal fluid PCR tests have become especially useful for diagnosing viral meningitis, with an estimated sensitivity of 95-100%. [26] Additionally, samples from the stool, urine, blood and throat can also help to identify viral meningitis. [24] CSF vs serum c-reactive protein and procalcitonin have not been shown to elucidate whether meningitis is bacterial or viral. [16]

In certain cases, a CT scan of the head should be done before a lumbar puncture such as in those with poor immune function or those with increased intracranial pressure. [1] If the patient has focal neurological deficits, papilledema, a Glasgow Coma Score less than 12, or a recent history of seizures, lumbar puncture should be reconsidered. [16]

Differential diagnosis for viral meningitis includes meningitis caused by bacteria, mycoplasma, fungus, and drugs such as NSAIDS, TMP-SMX, IVIG. Further considerations include brain tumors, lupus, vasculitis, and Kawasaki disease in the pediatric population. [16]

Treatment

Aciclovir Aciclovir 2D structure.svg
Aciclovir

Because there is no clinical differentiation between bacterial and viral meningitis, people with suspected disease should be sent to the hospital for further evaluation. [1] Treatment for viral meningitis is generally supportive. Rest, hydration, antipyretics, and pain or anti-inflammatory medications may be given as needed. [27] However, if there is initial uncertainty as to whether the meningitis is bacterial or viral in origin, empiric antibiotics are often given until bacterial infection is ruled out. [16]

Herpes simplex virus, varicella zoster virus and cytomegalovirus have a specific antiviral therapy. For herpes the treatment of choice is aciclovir. [28] If encephalitis is suspected, empiric treatment with IV aciclovir is often warranted. [16]

Surgical management is indicated where there is extremely increased intracranial pressure, infection of an adjacent bony structure (e.g. mastoiditis), skull fracture, or abscess formation. [12]

The majority of people that have viral meningitis get better within 7–10 days. [29]

Epidemiology

From 1988 to 1999, about 36,000 cases occurred each year. [30] As recently as 2017, the incidence in the U.S. alone increased to 75,000 cases per year for enteroviral meningitis. [10] With the advent and implementation of vaccinations for organisms such as Streptococcus pneumoniae, Haemophilus influenza type B, and Neisseria meningitis, rates of bacterial meningitis have been in decline, making viral meningitis more common. [16] Countries without high rates of immunization still carry higher rates of bacterial disease. [16] While the disease can occur in both children and adults, it is more common in children. [1] Rates of infection tend to reach a peak in the summer and fall. [31] During an outbreak in Romania and in Spain viral meningitis was more common among adults. [32] While, people aged younger than 15 made up 33.8% of cases. [32] In contrast in Finland in 1966 and in Cyprus in 1996, Gaza 1997, China 1998 and Taiwan 1998, the incidence of viral meningitis was higher among children. [33] [34] [35] [36]

Recent research

It has been proposed that viral meningitis might lead to inflammatory injury of the vertebral artery wall. [37]

The Meningitis Research Foundation is conducting a study to see if new genomic techniques can improve the speed, accuracy and cost of diagnosing meningitis in children in the UK. The research team will develop a new method to be used for the diagnosis of meningitis, analysing the genetic material of microorganisms found in CSF (cerebrospinal fluid). The new method will first be developed using CSF samples where the microorganism is known, but then will be applied to CSF samples where the microorganism is unknown (estimated at around 40%) to try and identify a cause. [38] There is also research investigating whether high-throughput sequencing, wherein the investigator does not need to compare DNA results with known genomic sequences, could be used in specifically diagnosing unknown causes of viral meningitis. [39]

While there is some emerging evidence that bacterial meningitis may have a negative impact on cognitive function, there is no such evidence for viral meningitis. [40]

Related Research Articles

<span class="mw-page-title-main">Encephalitis</span> Inflammation of the brain

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

<span class="mw-page-title-main">Varicella zoster virus</span> Herpes virus that causes chickenpox and shingles

Varicella zoster virus (VZV), also known as human herpesvirus 3 or Human alphaherpesvirus 3 (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles in adults but rarely in children. VZV infections are species-specific to humans. The virus can survive in external environments for a few hours.

<span class="mw-page-title-main">Lumbar puncture</span> Procedure to collect cerebrospinal fluid

Lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a lumbar puncture is to help diagnose diseases of the central nervous system, including the brain and spine. Examples of these conditions include meningitis and subarachnoid hemorrhage. It may also be used therapeutically in some conditions. Increased intracranial pressure is a contraindication, due to risk of brain matter being compressed and pushed toward the spine. Sometimes, lumbar puncture cannot be performed safely. It is regarded as a safe procedure, but post-dural-puncture headache is a common side effect if a small atraumatic needle is not used.

<span class="mw-page-title-main">Shingles</span> Viral disease caused by the varicella zoster virus

Shingles, also known as herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. Two to four days before the rash occurs there may be tingling or local pain in the area. Other common symptoms are fever, headache, and tiredness. The rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which can last for months or years, a condition called postherpetic neuralgia (PHN). In those with poor immune function the rash may occur widely. If the rash involves the eye, vision loss may occur.

<span class="mw-page-title-main">Aseptic meningitis</span> Medical condition

Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures. Aseptic meningitis is caused by viruses, mycobacteria, spirochetes, fungi, medications, and cancer malignancies. The testing for both meningitis and aseptic meningitis is mostly the same. A cerebrospinal fluid sample is taken by lumbar puncture and is tested for leukocyte levels to determine if there is an infection and goes on to further testing to see what the actual cause is. The symptoms are the same for both meningitis and aseptic meningitis but the severity of the symptoms and the treatment can depend on the certain cause.

<span class="mw-page-title-main">Viral encephalitis</span> Medical condition

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

<span class="mw-page-title-main">Meningoencephalitis</span> Medical condition

Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain tissue.

<span class="mw-page-title-main">Ventriculitis</span> Inflammation of the ventricles in the brain

Ventriculitis is the inflammation of the ventricles in the brain. The ventricles are responsible for containing and circulating cerebrospinal fluid throughout the brain. Ventriculitis is caused by infection of the ventricles, leading to swelling and inflammation. This is especially prevalent in patients with external ventricular drains and intraventricular stents. Ventriculitis can cause a wide variety of short-term symptoms and long-term side effects ranging from headaches and dizziness to unconsciousness and death if not treated early. It is treated with some appropriate combination of antibiotics in order to rid the patient of the underlying infection. Much of the current research involving ventriculitis focuses specifically around defining the disease and what causes it. This will allow for much more advancement in the subject. There is also a lot of attention being paid to possible treatments and prevention methods to help make this disease even less prevalent and dangerous.

A neurotropic virus is a virus that is capable of infecting nerve tissue.

<span class="mw-page-title-main">Mollaret's meningitis</span> Medical condition

Mollaret's meningitis is a recurrent or chronic inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. Since Mollaret's meningitis is a recurrent, benign (non-cancerous), aseptic meningitis, it is also referred to as benign recurrent lymphocytic meningitis. It was named for Pierre Mollaret, the French neurologist who first described it in 1944.

The central nervous system (CNS) controls most of the functions of the body and mind. It comprises the brain, spinal cord and the nerve fibers that branch off to all parts of the body. The CNS viral diseases are caused by viruses that attack the CNS. Existing and emerging viral CNS infections are major sources of human morbidity and mortality.

<span class="mw-page-title-main">Meningitis</span> Inflammation of the membranes around the brain and spinal cord

Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasionally photophobia.

<span class="mw-page-title-main">Herpes meningitis</span> Medical condition

Herpes meningitis is inflammation of the meninges, the protective tissues surrounding the spinal cord and brain, due to infection from viruses of the Herpesviridae family - the most common amongst adults is HSV-2. Symptoms are self-limiting over 2 weeks with severe headache, nausea, vomiting, neck-stiffness, and photophobia. Herpes meningitis can cause Mollaret's meningitis, a form of recurrent meningitis. Lumbar puncture with cerebrospinal fluid results demonstrating aseptic meningitis pattern is necessary for diagnosis and polymerase chain reaction is used to detect viral presence. Although symptoms are self-limiting, treatment with antiviral medication may be recommended to prevent progression to Herpes Meningoencephalitis.

<span class="mw-page-title-main">Herpes simplex encephalitis</span> Encephalitis associated with herpes simplex virus

Herpes simplex encephalitis (HSE), or simply herpes encephalitis, is encephalitis due to herpes simplex virus. It is estimated to affect at least 1 in 500,000 individuals per year, and some studies suggest an incidence rate of 5.9 cases per 100,000 live births.

Neurovirology is an interdisciplinary field which represents a melding of clinical neuroscience, virology, immunology, and molecular biology. The main focus of the field is to study viruses capable of infecting the nervous system. In addition to this, the field studies the use of viruses to trace neuroanatomical pathways, for gene therapy, and to eliminate detrimental populations of neural cells.

<span class="mw-page-title-main">Lymphocytic pleocytosis</span> Increase in lymphocytes within cerebrospinal fluid

Lymphocytic pleocytosis is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid (CSF). It is usually considered to be a sign of infection or inflammation within the nervous system, and is encountered in a number of neurological diseases, such as pseudomigraine, Susac's syndrome, and encephalitis. While lymphocytes make up roughly a quarter of all white blood cells (WBC) in the body, they are generally rare in the CSF. Under normal conditions, there are usually less than 5 white blood cells per µL of CSF. In a pleocytic setting, the number of lymphocytes can jump to more than 1,000 cells per µL. Increases in lymphocyte count are often accompanied by an increase in cerebrospinal protein concentrations in addition to pleocytosis of other types of white blood cells.

<span class="mw-page-title-main">Chronic meningitis</span> Inflammation of the membranes surrounding the brain and spinal cord lasting longer than 4 weeks

Chronic meningitis is a long-lasting inflammation of the membranes lining the brain and spinal cord. By definition, the duration of signs, symptoms and inflammation in chronic meningitis last longer than 4 weeks. Infectious causes are a leading cause and the infectious organisms responsible for chronic meningitis are different than the organisms that cause acute infectious meningitis. Tuberculosis and the fungi cryptococcus are leading causes worldwide. Chronic meningitis due to infectious causes are more common in those who are immunosuppressed, including those with HIV infection or in children who are malnourished. Chronic meningitis sometimes has a more indolent course than acute meningitis with symptoms developing more insidiously and slowly. Also, some of the infectious agents that cause chronic infectious meningitis such as mycobacterium tuberculosis, many fungal species and viruses are difficult to isolate from the cerebrospinal fluid making diagnosis challenging. No cause is identified during initial evaluation in one third of cases. Magnetic resonance imaging (MRI) of the brain is more sensitive than computed tomography and may show radiological signs that suggest chronic meningitis, however no radiological signs are considered pathognomonic or characteristic. MRI is also normal in many cases further limiting its diagnostic utility.

<span class="mw-page-title-main">Meningitis-retention syndrome</span> Meningitis-retention syndrome, a new medical category appeared in PubMed and other sources

Meningitis-retention syndrome (MRS) a combination of acute aseptic meningitis and urinary retention is a newly-recognized inflammatory neurological condition, therefore the prevalence remains still unknown.

References

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  36. ↑ "1996—Viral meningitis in Cyprus". WHO. Archived from the original on July 10, 2004.
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