Meningitis

Description

Meningitis is an acute or chronic inflammatory condition characterised by infiltration of the pia, arachnoid, and cerebrospinal fluid (CSF). The disease is primarily classified into acute pyogenic (bacterial), lymphocytic (viral), and chronic (tubercular or granulomatous) forms. The term leptomeningitis or infectious meningitis is also sometimes used to describe this condition.

Pathogenesis & Subtypes

The pathogenesis of meningitis varies depending on the subtype:

• Bacterial meningitis often follows a hematogenous spread from a remote infection, such as in the heart or teeth. Occasionally, direct extension from an adjacent infection (e.g., sinusitis, otitis media) or a penetrating injury may lead to bacterial meningitis.
• Viral meningitis, also known as aseptic meningitis, is often caused by enteroviruses. It can also result from mumps, herpes simplex virus, and several other viruses.
• Fungal meningitis is less common and typically affects individuals with compromised immune systems. Fungi such as Cryptococcus neoformans and Coccidioides immitis are typical causative agents.
• Tuberculous (TB) meningitis is a chronic form of the disease caused by Mycobacterium tuberculosis. The bacteria reach the meninges via the bloodstream from a primary focus elsewhere in the body.

Epidemiology, Risk Factors & Associations

Meningitis can affect individuals of all ages, with variations in causative organisms across different age groups. The incidence of bacterial meningitis has increased over the past 30 years, largely due to nosocomial infections (approximately 3 per 100,000 in the UK). Meningitis is most common in children and adolescents, whereas viral meningitis predominantly affects infants and elderly individuals. Cryptococcal meningitis is most often seen in individuals with AIDS, representing the most common fungal disease of the central nervous system in this population.

Risk factors for meningitis include a weakened immune system, recent head injury or neurosurgery, chronic illnesses such as diabetes, and certain geographical regions (for example, the meningitis belt in Africa). Individuals living in close quarters, such as military barracks or university dormitories, are also at higher risk.

Acute Pyogenic Meningitis	Infants	E. Coli or group B streptocci
	Young adults	N. meningitidis
	Older adults	S. Pneumonia or L. monocytogenes
Chronic Meningitis		Mycobacterium tuberculosis

Clinical Features

• The hallmark clinical features of meningitis include a severe headache, fever, and nuchal rigidity.
• Additional symptoms often include photophobia, nausea, vomiting, and altered mental status.
• In adults, Brudzinski’s and Kernig’s signs—both indicative of meningeal irritation—may be positive.
• For children and infants, clinical presentation can include irritability, lethargy, and poor feeding.

Complications

Meningitis can result in numerous complications, both infectious and vascular.

• Infectious complications include cerebritis, abscess formation, ventriculitis, and formation of subdural fluid collections (either sterile effusions or purulent empyema).
• Vascular complications can arise from arterial spasm or infectious arteritis, leading to ischemic brain damage. Moreover, dural venous sinus thrombosis may occur.
• More severe outcomes include cerebral oedema, raised intracranial pressure, and in some cases, death.

Subtypes

Meningitis can be classified into several subtypes based on the causative agent:

• Acute pyogenic meningitis, most often caused by bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae.
• Lymphocytic or aseptic meningitis, generally due to a viral infection.
• Chronic meningitis, often resulting from tuberculous or granulomatous infections.

Subtypes

Meningitis can be broadly classified based on the causative agent. Each subtype has distinct epidemiology and clinical features:

• Bacterial meningitis: This is a serious, potentially life-threatening condition caused by bacteria. Streptococcus pneumoniae (responsible for up to 50% of cases), Neisseria meningitidis (10%-25%), and Haemophilus influenzae (<5%) are the most common culprits. Newborns are susceptible to infections by Group B Streptococcus, Escherichia coli, and less frequently, Listeria monocytogenes.
• Viral meningitis: More common and typically less severe than bacterial meningitis, it’s primarily caused by non-polio enteroviruses (up to 90% of cases). Other viruses such as herpes simplex virus, mumps virus, and human immunodeficiency virus (HIV) can also cause viral meningitis. Incidence varies greatly by geographical region and season, but it is estimated to be between 26 and 37 cases per 100,000 population in the U.S.
• Fungal meningitis: This is relatively rare, predominantly affecting individuals with compromised immune systems. Cryptococcus neoformans is the most common cause, especially in patients with HIV/AIDS, accounting for around 70%-90% of fungal meningitis cases in this population. The incidence of cryptococcal meningitis among people with HIV is approximately 0.4–1.3% in Western countries and 3–13% in Africa.
• Tuberculous meningitis: Caused by Mycobacterium tuberculosis, this subtype can be challenging to diagnose and treat. It accounts for approximately 1%-5% of all TB cases and approximately 15% of extrapulmonary TB cases. The highest incidence is in regions where TB is endemic, such as Southeast Asia and Sub-Saharan Africa.
• Parasitic meningitis: This subtype is extremely rare, and its incidence is not well-studied. Certain parasites like Naegleria fowleri and Angiostrongylus cantonensis can invade the central nervous system and cause meningitis.
• Non-infectious meningitis: This subtype includes conditions where meningitis results from non-infectious causes such as drugs, autoimmune diseases, and cancers. For example, neoplastic meningitis affects approximately 5-8% of patients with solid and hematological malignancies. Drug-induced aseptic meningitis is a rare adverse effect of certain medications, with an unknown incidence.

Pathological Features

Histopathology

Microscopic examination of cerebrospinal fluid (CSF) typically shows increased white blood cells (leukocytosis), elevated protein levels, and decreased glucose—classic signs of infectious meningitis. The specific cellular makeup of the CSF can also provide clues about the causative agent: bacterial meningitis is typically marked by a predominance of neutrophils, while viral meningitis often shows lymphocytic predominance.

Serology

Serological tests can be used to identify the specific causative organism of meningitis. These can include cultures, antigen detection tests, and polymerase chain reaction (PCR) testing.

Biochemistry

Biochemical analysis of CSF can provide crucial information in the diagnosis of meningitis. A decrease in CSF glucose and an increase in protein are often seen in bacterial meningitis, while viral meningitis typically presents with normal glucose and mildly elevated protein levels.

Genetics

While there are no specific genetic mutations directly linked to meningitis, certain genetic factors can influence an individual’s susceptibility to the disease.

Radiological Features

MRI

• T1-weighted imaging (T1WI): Isointense exudate.
• T1WI C+: Enhancement of the exudate and the pial surface of the brain.
• T2-weighted imaging (T2WI): Hyperintense exudate.
• Diffusion-weighted imaging (DWI): Highly useful for detecting complications such as empyema, abscess, and ventriculitis.
• Fluid-attenuated inversion recovery (FLAIR) MRI: Hyperintense signal in sulci and cisterns. Delayed contrast-enhanced FLAIR is often the most sensitive sequence for detecting leptomeningeal disease.

CT

• Non-contrast CT: Findings may vary from normal to acute hydrocephalus and increased density in the basal cisterns or sylvian fissures due to inflammatory debris, which may simulate subarachnoid haemorrhage.
• Contrast-enhanced CT: May show enhancement of the meninges, indicative of inflammation.

Grading and Staging

No specific staging or grading system exists for meningitis. The severity of the disease is typically assessed based on the clinical symptoms, CSF analysis, and imaging findings.

Diagnosis

The diagnosis of meningitis primarily relies on clinical symptoms and CSF analysis. While imaging can provide valuable information about the condition and its complications, it is not typically used as the primary diagnostic tool. The definitive diagnosis is made by identifying the causative organism in the CSF through culture or PCR testing.

Differential Diagnosis

• Encephalitis: Typically presents with focal neurological deficits or seizures, which are less common in meningitis.
• Brain abscess: Can cause symptoms similar to meningitis, but usually localised to a specific region of the brain.
• Subarachnoid haemorrhage: The headache associated with this condition is typically sudden and severe, often described as a ‘thunderclap’ headache. CT scan can help differentiate between this condition and meningitis.
• Migraine: Recurrent episodes of severe headache, often with accompanying symptoms such as photophobia, phonophobia, and nausea.
• Chemical Meningitis: Can result from a ruptured dermoid cyst.

Management

Management of meningitis typically involves a multidisciplinary team, including infectious disease specialists, neurologists, and sometimes neurosurgeons. The mainstay of treatment is intravenous antibiotics, with the choice of therapy based on the age of the patient and the suspected causative organism. Supportive care, including pain management and fever control, is also essential. In some cases, such as when there is significant cerebral oedema or a large abscess, surgical intervention may be necessary. The typical next step after diagnosis is a lumbar puncture to collect CSF for analysis. The next steps depend on the causative organism, the severity of the disease, and the patient’s overall health status.