Introduction

People of all ages are susceptible to meningitis and its many complications, some of which can be life-threatening. Ischemic strokes are expected to occur in a quarter of people diagnosed with bacterial meningitis.¹ Most common in younger children, meningitis is an inflammation of the layers of protective membranes, also known as meninges, surrounding the brain and spinal cord often due to a primary infection.² This inflammation puts immense pressure on the spinal cord or brain, reducing the circulation of blood and cerebrospinal fluid (CSF). The primary infection can be caused by various microbes: bacteria, viruses, fungi, and parasites. However, the causes of meningitis are not limited to infectious diseases. Non-infectious causes include cancer, chemical irritation, medication/ drug use, autoimmune diseases, and physical injury. Nonetheless, they all share similar symptoms:

• Headache due to intracranial pressure
• Fever is seen in bacterial and viral meningitis 
• Neck stiffness due to the inflammation of the meninges 
• Sensitivity to light
• Cognitive impairment
• Skin rash that does not fade when pressure is applied (petechiae)

Differentiating the different types of meningitis is a pivotal step in the diagnostic process that must precede treatment as the standard treatment for one type of meningitis may be futile for the treatment of another. With the appropriate treatment, we can prevent the onset of sepsis, a life-threatening complication where the immune system attacks its own organs during an infection.³ Hence, this article aims to provide a comprehensive overview of the distinctive characteristics of each type of meningitis, in hopes of better improving our understanding of the infection and its implications.

Bacterial meningitis

Though it is not as common as viral meningitis, bacterial meningitis is significantly more life-threatening.⁴ According to the CDC, a person diagnosed with bacterial meningitis requires immediate medical treatment to prevent the rapid onset of serious complications.⁵ People become infected with bacteria like Streptococcus pneumoniae and Neisseria meningitidis through respiratory droplets from another person’s cough or sneeze near them, kissing, or close contact with someone who is already infected.⁶ Most concerningly, meningitis in pregnant women can rapidly lead to foetal or maternal death.⁷ In fact, children under the age of 2 are at the highest risk, followed by the risk factors of the winter season, people who are immunocompromised and smoking to list a few. As well as ischemic stroke, hearing loss is observed in 34% of cases of bacterial meningitis- 19% of whom are infants. Non-neurological complications include amputations, hydrocephalus, and learning difficulties.¹

Diagnosis of meningitis always involves a lumbar puncture, a procedure where a needle is inserted into the lower back to collect a small CSF sample from the vertebral canal.⁸ While the opening pressure is quantified when the needle is inserted, the CSF sample is then analysed for its appearance, white blood cell count, glucose and protein levels.⁹ Depending on which type of meningitis is present, the overall results will vary. In bacterial meningitis, the following results are expected:

• Elevated opening pressure 
• Clear, cloudy, or purulent colour
• High white blood cell count (>100 cells/µl)
• Low glucose levels
• Elevated protein levels ^9-10

It is also expected that the CSF is cultured for Gram staining. If the culture appears purple, it is a Gram-positive bacteria (e.g. Streptococcus pneumoniae) but, if it is pink, then it is a Gram-negative bacteria (e.g. Haemophlius influenzae). This distinction is required as the efficacy of antibiotics varies between Gram-positive and Gram-negative bacteria. For the treatment of bacterial meningitis, antibiotics are the standard treatment before, during and after identifying the bacteria causing meningitis. 

• Streptococcus pneumoniae: if the patient is resistant or allergic to penicillin, they are given ceftriaxone or cefotaxime with vancomycin 
• Haemophilus influenzae: ceftriaxone or cefotaxime 
• Neisseria meningitides: if the patient is resistant or allergic to penicillin, they are given ceftriaxone or cefotaxime 
• Listeria monocytogenes: ampicillin/amoxicillin or co-trimoxazole¹¹

Viral meningitis 

Though not as severe as bacterial meningitis, viral meningitis has become the most common type of meningitis. Viral meningitis can also be transmitted through close contact with an infected person. Enteroviruses and HIV are the most predominant causes of viral meningitis. While HIV meningitis mostly affects women in their mid-30s, enterovirus meningitis dominates across all age groups.^12,13 Therefore, the risk factors also differ from those associated with bacterial meningitis. 

• Sexual history
• Travel abroad
• Exposure to rodents or ticks
• People with weak immune systems, particularly young children¹⁴

Undermining the risk factors during a clinical examination can help healthcare professionals better diagnose the type of meningitis or viral meningitis at play. A CSF analysis positive for viral meningitis should show:

• Normal or elevated opening pressure
• Clear colour
• High white blood cell count (10-1000 cells/µl)
• Normal glucose levels
• Elevated protein levels^9,10

Alongside the tests conducted on the CSF sample, polymerase chain reaction (PCR) analysis of the CSF is considered the gold standard for diagnosing the specific virus as it has a 100% sensitivity in detecting viral genetic material.¹⁴ Where treatment is an immediate requirement in bacterial meningitis, viral meningitis is expected to resolve on its own in most cases. Either way, the best treatment for viral meningitis is prevention as current treatment involves supportive care; in mild cases, fluids, bed rest and pain management are offered. However, antiviral treatment will be considered if symptoms don't improve.¹²

Fungal meningitis 

Fungal meningitis is rare in comparison to bacterial and viral meningitis, and it typically occurs if an initial fungal infection spreads to the brain or spinal cord. Contrary to the previous types of meningitis described, this type of meningitis is spread through inhalation of fungal spores commonly found in soil. Cryptococcus, most commonly caused by fungal meningitis, is one of a few fungi that infect immunosuppressive people.¹⁵ People who take medications such as steroids that weaken the immune system have an elevated risk,¹⁶ increasing the risk of mortality or morbidity due to the complications of ischemic strokes¹⁷ and heightened intracranial pressure.¹⁸

While a lumbar puncture is required to obtain the CSF and isolate any fungi, a review has stated that 25-30% of fungal meningitis cases have had normal CSF results.¹⁹ However the following is usually expected:

• Elevated opening pressure
• Clear or cloudy colour
• Moderately high white blood cell count (10-500 cells/µl)
• Low glucose levels 
• Elevated protein levels⁹

Hence an India Ink stain is often conducted, identical to a Gram stain, to identify cryptococcal meningitis.²⁰ The diagnostic process is arguably easier than treatment. The ideal treatment consists of a combination of amphotericin and flucytosine to prevent any drug-resistant reactions and improve survival efficacy. In reality, many people affected by cryptococcal meningitis where it is most prevalent do not have access to the latter medication- especially when it can reduce the risk of mortality by roughly 40%.²¹ Otherwise, people opt to manage the intracranial pressure by elevating their head by 30° and having excess CSF removed through the process of therapeutic lumbar puncture.²²

Parasitic meningitis

In addition to fungal meningitis, parasitic meningitis is also one of the rare types; in this case, it normally affects animals. Hence, parasitic meningitis in humans occurs when they eat contaminated or infected food like snails or freshwater fish.²³ Generally, it is caused by the parasitic worm Angiostrongylus cantonensis found in infected rodents²⁴ followed by Baylisascaris procyonis (found in infected raccoons)²⁵ and Gnathostoma spinigerum (found in undercooked or raw freshwater fish, eels, frogs, birds, and reptiles).²⁶ Though it usually resolves by itself in 4-6 weeks and is rarely fatal,²⁷ it can still cause complications like eye and facial paralysis. Nonetheless, people gain control of their muscles again over time.²⁸ A case of parasitic meningitis is treated with pain management like therapeutic lumbar puncture and possibly corticosteroids to reduce inflammation.²⁹

Non-infectious meningitis 

Not as prevalent as the previous types, non-infectious meningitis stems from diverse causes. The most common causes are:

• Side effects of medication 
• Autoimmune diseases
• Complications of cancer if cancer cells metastasize to the meninges or trigger an inflammatory response
• Physical injury to the head or spine directly leads to inflammation of the meninges³⁰

The risk factors often mirror those of the underlying conditions. Hence, following a thorough physical examination, the individual is treated accordingly with the underlying cause in mind. For instance, treatment for carcinomatous meningitis is complicated and unique to each patient in the context of the severity of their cancer; if the risks of standard cancer treatment outweigh the benefits, palliative care may be recommended instead.³¹ If the meningitis is caused by a medication, then a healthcare professional may discuss discontinuing the medication and finding an alternative plan to treat the primary condition. 

Summary 

Meningitis can be a deadly infection, mostly causing a burden in the younger population. Ultimately, diagnosis is the most important part as it confirms which type of meningitis is involved. While bacterial meningitis urges immediate treatment to prevent further severe complications or mortality, the other types of meningitis are often expected to resolve on their own and may only need supportive care or therapeutic lumbar puncture. Nonetheless, treatment gets more complex if the patient is suffering from non-infectious meningitis as it may be difficult to identify the underlying cause or treat the underlying cause safely yet effectively. With early detection solidified, the future goal in meningitis treatment is to identify strategies that may be less invasive and time-efficient so that the onset of the severe complications can be prevented.