Meningitis – Causes, Symptoms and Treatment

Meningitis – Causes, Symptoms and Treatment

Meningitis is a clinical syndrome characterized by inflammation of the meninges. The meninges are connective tissue membranes that line the skull and vertebral column and enclose the brain and the spinal cord.

The meninges consist of the following:

1. Dura: a tough but inelastic outer membrane also known as the pachymeninx.
2.  Arachnoid: a lacy web-like middle membrane.
3. Pia: the innermost layer.

Inflammation of the Dura is referred to as pachymeningitis which is less common while the inflammation of the Pia matter and Arachnoid tissue is called leptomeningitis.

Brief History

As far back as ancient Greece, meningitis may have been known when Hippocrates (C.460BC-370BC) described conditions central to the disease.

A Persian Physician, Avicenna   (c.AD980-AD1037) revealed more about it in his recorded observations. Between 1714- 1766.  A Scottish physician Robert Whytt described “dropsy of the brain” (now known as tuberculosis meningitis) in a post- humus report. However there was no link established between the condition and an agent that causes it. Then came an Australian pathologist and bacteriologist: Anton Weichselbaum (1845- 1920) who found the agent of meningitis. In 1887, he specifically called it meningococcus.

Epidemiology

Distribution:

Meningitis has only recently manifested itself as an epidemic but the first recorded one occurred in Geneva, Switzerland in 1805. A major case of epidemic meningitis swept through what’s today known as Nigeria and Ghana from 1905-1908. Meningitis is however, endemic in parts of Africa, India and other developing countries because of less access to preventive services such as vaccination. An incident rate that is tenfold higher than that in developed countries has been reported.

Race:

It affects people of all races. In United States, blacks have a higher reported rate of meningitis than white people and Hispanic people.

Age:

Though it affects people of all age groups; infants, young children (<5yrs) and elderly individuals (>60yrs) are more susceptible.

Sex:

In neonates, the ratio of male to female is about 3:1.

Morbidity and Mortality:

This will depend on the pathogen, patients’ age, condition and severity of acute illness. Among bacterial pathogens, pneumococcal meningitis causes the highest rate of morbidity and mortality.

Risk factors

1. Age: patients at extremes of life are more at risk. E.g. Age greater than 60yrs and age of 5yrs or less.
2. Intravenous Drug Abuse.
3. Splenectomy and sickle cell disease which increases the risk of meningitis secondary to encapsulated organisms.
4. Alcohol and cirrhosis.
5. Contiguous infection (sinusitis).
6. Dural defect (e.g. traumatic, surgical, congenital).
7. Bacterial endocarditis.
8. Thalassemia major.
9. Ventriculo-peritoneal shunt.
10. Malignancy
11. Some cranial congenital deformities.
12. Crowding (e.g. military recruits) increases the risk of outbreak of meningococcal meningitis.
13. Immunosuppression increases the risk of opportunistic and acute bacterial meningitis.
14. HIV infection which predisposes to bacterial meningitis caused by encapsulated organisms primarily streptococcus pneumoniae and opportunistic pathogens.
15. Diabetes mellitus, renal or adrenal insufficiency, hypoparathyroidism or cystic fibrosis.

Etiology

The causes of meningitis include the following:

1. Direct contagious spread.
2. Non- infectious causes.
3. Infectious agent.

Direct contagious spread

This may include sinusitis, otitis media, and direct inoculation during intracranial manipulation, trauma and congenital malformation. Patients with any of these are at a risk for bacterial meningitis.

Non- infectious causes

1. Cancer (sarcoidosis).
2. Polyarteritis nodosa
3. Rheumatoid arthritis.
4. Toxins.
5. Malignancies.
6. Diseases such as Systemic Lupus Erythematosus (SLE).
7. Drugs (Antibiotics, NSAID’S, Antimicrobials e.g. trimethroprim sulfamethoxazole).

Infectious agents

Infectious agents that cause meningitis can be divided into two:

1. Non- bacterial causes.
2. Bacterial causes.

Non- Bacterial Causes

This includes the viral, fungal and parasitic organisms.

Viral meningitis

This refers to meningitis caused by viral infection; it is commonly caused by enteroviruses. Some viral organisms include:

I.        Human immunodeficiency virus.

II.        Herpes simplex virus (HSV) type I and II

III.        Varicella- zoster virus.

IV.        Epstein- Barr virus.

V.        Cytomegalovirus.

VI.        Polio virus.

1. Mumps virus.
2. West Nile virus

IX.        Coxsackie virus A and B.

X.        Human herpes virus.

XI.        Lymphocytic choriomeningitis virus (LCM).

1. Rubella virus.

Signs and Symptoms

I.        Babies have a more gradual illness, refusal to eat, sleepier than usual and fussy.

II.        Babies younger than 18months may develop a rigid or tender back and extreme fussiness that cannot be consoled.

III.        In some cases, rash may cover most of the body or arms and legs.

IV.        In enterovirus meningitis, conjunctivitis and sore throat may occur.

Other signs may include:

Muscle weakness, tiredness, headache, muscle spasms, insomnia and inability to concentrate.

These are rarely permanent but may take a few weeks to months to disappear.

Diagnosis

• Ø This is based on clinical history compatible with meningitis and a physical examination in which pain is elicited upon flexing the neck. Often a patient with meningitis will have so much pain that the neck will be rigid.
• Ø Spinal tap.
• Ø Blood test.

Treatment

In some cases, there’s no treatment.

I.        Only acetaminophen should be given to reduce fever.

II.        Clear food should be offered.

III.        During recovery, a child needs rest in a darkened quiet room.

IV.        Specific antiviral can be given to patients with Varicella- Zoster, Herpes simplex and cytomegalovirus.

Prevention

1. Personal hygiene.

B.    Fungal meningitis

Causative organisms include:

I.        Crytococcus neoformans.

II.        Coccidiodes immitis.

III.        Blastomyces dermatidis.

IV.        Histoplasma capsulatum.

V.        Candida albicans.

VI.        Aspergillus spp.

1. Sporothrix schenekii.

C.    Parasitic Meningitis

Parasites include:

I.        Schistosoma spp.

II.        Strongyloides stecoralis

III.        Naegleria Fowleri

IV.        Echinococcus granulosis

V.        Taenia solium

Bacterial Agents

This is the most abundant, common and major cause of meningitis. It is divided into three (3) classes viz:

1. Acute bacterial meningitis.
2. Sub- acute bacterial meningitis.
3. Chronic bacterial meningitis.
4. A.  Acute Bacterial Meningitis

This type doesn’t last long and is characterized by an acute onset of meningeal symptoms and Neutrophilic Pleocytosis. Some bacteria that cause acute meningitis include:

I.        Haemophilus Influenzae type b (Hib)

II.        Listeria Monocytogenes.

III.        Streptococcus Pneumoniae (Pneumococcus)

IV.        Neisseria Meningitidis (meningococcus)

V.        Pseudomonas Aeruginosa

VI.        Staphylococcus Spp.

Before the 1990’s, Hib was the leading cause of bacterial meningitis but new

Vaccines being given to children as immunization have reduced the occurrence of serious Hib disease. Today, Neisseria Meningitidis and Streptococcus Pneumoniae are the leading causes.

1. B.  Sub- Acute Bacterial Meningitis.

Approximately 75% of bacterial meningitis is sub- acute. Its symptoms begin several days prior. Ill patients still require urgent ED diagnosis and care to prevent further decompensation. 

1. C.  Chronic Bacterial Meningitis

This is a constellation of signs and symptoms of meningeal irritation associated with CSF pleocytosis that persists for a long time usually longer than 4weeks. Some bacteria include:

I.        Mycobacterium Tuberculosis.

II.        Actinomyces Spp

III.        Nocardia Spp

IV.        Tryponema Pallidum

V.        Brucella Spp

VI.        Francisella Tularensis

Diagnosis of Bacterial Meningitis

Spinal tap: a process of collection of CSF from the spinal canal.

Treatment:

1. Antibiotic therapy including powerful antibiotics such as ceftriaxone (Rocephin) and vancomycin (Vancoan).
2. Anticonvulsant medications such as Dilantin (phenytoin) to prevent seizures in several meningitis.
3. Anti- nausea medication if needed.
4. Corticosteroids to help reduce inflammation and swelling.
5. Fever reducing medications such as acetaminophen (Tylenol). Aspirin use should be avoided in children.
6. Sedatives to increase comfort if needed.
7. Surgical drainage of sinus if needed.

Asceptic (Non- Pyogenic) Meningitis

This is so- called if its cause is not apparent after initial evaluation. An example of this is mollaret syndrome which is a recurrent but benign aseptic meningitis syndrome caused by Herpes Simplex Virus (HSV).

This is non- pyogenic meningitis is caused by bacteria, fungi, mycobacteria and parasitic agents.

Pathogenesis

Animal models have proven to be extremely valuable in the study of the pathogenesis and pathophysiology of bacterial meningitis with the hope of providing new information that may lead to an improved outcome from this disorder.

Naturally, the brain is protected from the body’s immune system by a barrier the meninges create between the bloodstream and the brain. In meningitis, the barrier can become a problem because once bacteria or other organisms get into the brain, they spread.

When the body tries to fight the infection, the problem is worsened because the blood vessels become leaky and allow white blood cells to enter the brain and meninges causing swelling and eventually lead to decreased blood flow to parts of the brain worsening the symptoms of the infection.

These infectious agents (like bacteria) have 3 ways by which they get to the Central Nervous System (CNS) and cause the disease. They include:

1. Establishment of a localized infection in the host in the form of colonization of the skin nasopharynx, respiratory tract, genitourinary tract and or gastrointestinal tract. Most meningeal pathogens are transmitted through the respiratory tracts as exemplified by nasopharyngeal colonization with Streptococcus Pneumoniae.
2. Establishment is followed by invasion of the submucosa by circumventing host defenses.
3. CNS invasion through bloodstream causing bacteremia, viremia, fungemia and parasitemia or direct contagious spread via trauma, sinusitis, otitis media, congenital malformation etc or via a reterograde (olfactory and peripheral nerves) neuronal pathway E.g.Nagleria Fowleri.

Once inside the CNS, the infectious agent survives likely because of limited host defenses (like complement components and immunoglobulin) in this compartment. Meningeal inflammation is hence elicited because of uncontrolled presence and replication of the infectious agent.

Pathophysiology

The pathophysiology includes the pivotal role of cytokines: e.g. interleukin (IL) – 1, Tumor Necrosis factor – alpha (TNF –α); chemokines (IL -8) and other pro- inflammatory molecules in the pathogenesis of pleocytosis and neuronal damage during bacterial meningitis. Hence, increased level of cytokines in the CSF such as TNF- α, IL-6, IL-1 an IL- 8 are characteristic finding in patients with bacterial meningitis and cytokine level including those of IL- 6, TNF- α, interferon- ϒ have been found to be elevated in patients with aseptic meningitis. Events involving these inflammation mediators include:

1. Synthesis of cytokines and proinflammatory mediators due to exposure of the cells (e.g. leukocytes, microglia, astrocytes and meningeal macrophages) to bacterial products released during replication and death. This process is believed to be initiated by the ligation of bacterial components (e.g. peptidoglycan) to pattern recognition receptors such as the Toll- like receptors.
2. TNF- α and IL-1 amongst all cytokines released are the most prominent and is believed to mediate the inflammation cascade. IL-1 produced from activated mononuclear phagocytes is responsible for induction of fever during bacterial infections. Both IL-1 and TNF- α have been detected in the CSF of individuals with bacterial meningitis and appear early during the course of the disease and have been detected within 30- 45 minutes of intracisternal endotoxin inoculation.
3. Many secondary mediators such as IL-6, IL-8, Nitric oxide, Prostaglandins (PG.E₂) and Platelet activation factor (PAF) presumably amplify the inflammatory event either synergistically or independently. IL-6 induces acute phase reactants in response to bacterial infection while IL-8 mediates neutrophil chemo-attractant responses induced by TNF- α and IL-1. Nitric oxide when in high amounts can induce cytotoxicity. Prostaglandin, a product of cyclo- oxygnase (COX) appears to participate in the induction of increased blood brain barrier permeability. The precise role of all these secondary mediators in meningeal inflammation is unclear.
4. The net result of the above processes is vascular endothelial injury and increased blood brain barrier permeability leading to the entry of many blood components into the subarachnoid space. This contributes, in many patients, to elevated CSF protein level and vasogenic oedema.

In response to cytokines and chemotactic molecules, neutrophils migrate from the bloodstream and penetrate the damage blood brain barrier producing the profound Neutrophilic pleocytosis, a characteristic feature of bacterial meningitis. Products of bacterial degradation, neutrophils, and other cellular activation lead to cytotoxic oedema. Also interstitial oedema caused by CSF viscosity from the influx of plasma components into the subarachnoid space and diminished venous outflow.

1. The ensuing cerebral oedema (i.e. vasogenic, cytotoxic and interstitial) significantly contributes to intracranial hypertension and consequent decrease in cerebral blood flow. Anaerobic metabolism ensues leading to increased laclate concentration and decreased CSF glucose (hypoglycorrhachia) caused by decreased glucose transport into the spinal fluid compartment. This process if not controlled and modulated by effective treatment, a transcient neuronal dysfunction or permanent neuronal injury results.

However, attenuation of these inflammatory responses (E.g. by co-administration of anti-inflammatory agents) may diminish many of these pathophysiologic consequences of meningitis and perhaps improve morbidity and mortality from this disorder.

Morphological changes

The definitive diagnosis of meningitis is often made by analyzing a sample of CSF which is collected during a procedure known as spinal tap. In meningitis, the CSF shows some changes which either show the causative organism or confirms the disease. Such changes include:

1. Microbiological changes.
2. Hematological changes.
3. Pathological changes.

MICROBIOLOGICAL CHANGES

Here there is a mild or moderate increase in CSF protein and low sugar (glucose) level.

HEMATOLOGICAL CHANGES

There’s increases white blood cell count but on microscopic examination, neutrophils fill the subarachnoid space in severely affected areas and are found predominantly around the leptomeningeal blood vessels in less severe cases.

PATHOLOGICAL CHANGES

The inflammatory cells infiltrate the walls of leptomeningeal veins and may extend into the substance of the brain (focal cerebritis) in fulimant meningitis. Phlebitis may also lead to venous thrombosis and haemorrhagic infraction of the underlying brain.

The meningeal vessels are engorged and stand out prominently. In acute meningitis, an exudate is evident within the leptomeninges over the surface of the brain. The location of the exudate varies such as in H: Influenzae meningitis, it is usually basal while in pneumococcal meningitis it’s often densest over the cerebral convexities near the sagittal sinus.

Generally, the normal clear CSF becomes cloudy and sometimes frankly purulent and when allowed to stand, the CSF clots especially in bacterial meningitis.   

Clinical Manifestation and Complications

Clinical History

A clue into the clinical history of the patient suggests or may suggest a specific etiological agent. This clinical history entails;

1. History of exposure to a patient with a similar illness.
2. History of sexual contact and high risk behavior may suggest HSV and HIV- infections.
3. Exposure to rodents may suggest rabies and LCM virus.
4. A history of myalgias, fatigue and anorexia may suggest systemic viral infection.
5. Intake of unpasteurized milk may suggest brucellosis.
6. Presence of cochlear implants with a positioner has been associated with a higher risk of bacterial infection.
7. A history of recent cranial surgery may suggest Staphylococcus aureus and Pseudomonas aeruginosa infection.

Physical Examination

1. 1.   Brudzinski’s sign: passive neck flexion in a supine patient is accompanied by involuntary flexion of the hip and knees.
2. 2.   Cranial nerve palsies (iii, iv, vi, vii) maybe observed as a result of increased intracranial pressure or presence of exudates encasing the nerve roots.
3. 3.   Faecal neurologic signs as a result of ischaemia from vascular inflammation and thrombosis.
4. 4.   Lasegue’s sign: in a supine position with the hip flexed and knee extended, dorsiflexion of the ankle causes pain or muscle spasm in the posterior thigh.
5. 5.   Kerning’s sign: passive knee extension elicits neck pain and hamstring resistance in a supine patient.
6. 6.    Nuchal rigidity: This is resistance to passive flexion of the neck.
7. 7.   Papilloedema which is sign of increased intracranial pressure.
8. 8.   Sign of cerebral dysfunction are common including confusion, irritability, delirium and coma. These are usually accompanied by fever and photophobia.
9. 9.   Systemic findings: Physical examination may provide clues to the etiology e.g.s include:
10. Sinusitis or otitis suggests direct extension into the meninges.
11. Genital vesicles suggest HSV-2 meningitis.
12. Parotitis may suggest mumps.
13. Macules and petechiae that rapidly evolve into puerperal suggest meningococcemia.
14. Hepatosplenomegally and lymphadenopathy suggests a systemic disease including viral (HIV, CMV) and fungal (e.g. disseminated histoplasmosis) disease.

Diagnostic Tests

Patient may undergo the following:

1. Lumbar Puncture: in patient with meningitis, the CSF often shows a low sugar level along with an increased white blood cell count and increased protein. Lactate concentration in CSF is increased in bacterial but decreased in viral meningitis. CSF- chloride is decreased. Analysis of the CSF can help identify the exact bacterium that is causing the illness. An expert EV- test can be done and is specific for viral genetic materials in the CSF. A positive test indicates viral. The EV-test takes about 2 hrs.
2. Imaging: you can perform;
3. Computerized Tomography (CT) Scan of the chest, sinuses or skull may reveal swelling. If the patient is at risk for elevated intracranial pressure, a CT- Scan is preferred over lumbar puncture.
4. MRI-Scan is preferred over CT- Scan in patients at risk for elevated intracranial pressure which include those with recent head trauma, CNS neoplasm or focal neurologic deficits such as Papilloedema because of the superiority of MRI in demonstrating areas of cerebral oedema, ischaemia and meningeal inflammation.
5. A throat culture can be done to find and identify the bacteria causing throat pain, neck pain and headache. Others include:
6. CSF culture test
7. Gram staining
8. Blood cultures

Differential diagnosis

1. Brain abscess
2.  Febrile seizures
3. CNS vasculitis
4. Encephalitis
5. Meningeal carcinomatosis
6. Subarachnoid hemorrhage

Signs and symptoms

1. Pleocytosis
2. Photophobia
3. Seizures
4. Lethargy
5. Confusion and altered consciousness
6. Sleepiness
7. Phonophobia
8. Headache
9. Nuchal rigidity
10. Fever and chills
11. Sore throat
12. Vomiting.

Complications

The longer the disease without treatment, the greater the risk of complications which can be severe. These complications can either be neurological or non- neurological.

Non- Neurological

1. Venous sinus thrombosis
2. Septic or reactive pericarditis
3. Severe cerebral oedema
4. Arthritis
5. Kidney failure
6. Papilloedema
7. Thrombophlebitis
8. Peripheral gangrene

Neurological

1. Loss of hearing
2. Loss of speech
3. Blindness
4. Obstructive hydrocephalus
5. Learning disabilities
6. Brain damage
7. Paralysis
8. Behavioral or emotional problems such as depression, bed- wetting, aggression.

Infections may not progress into acute meningitis but could result in a fatal fulimnant septicaemia. An acute fulimnant septicaemia  in very young children could lead to haemorrhagic rash and bleeding into the adrenal glands resulting in “water-house Friderichsen syndrome” characterized by large, purple, blotchy skin nodules (petechiae) haemorrhages, vomiting and diarrhea, circulatory collapse, adrenal necrosis and death within 10- 12 hours. Bacterial infections of the CNS progresses quickly and within a matter of days, the disease can lead to shock and eventual death.

Treatment

1. If fungal meningitis is suspected, treatment of local pulmonary lesion should be commenced.
2. In viral meningitis, there’s no specific treatment and the condition is usually benign and self- limiting. The patient should be treated symptomatically in a quiet environment with fluid administration, analgesia and bed rest.
3. Patients showing signs or symptoms of meningitis should seek medical attention immediately.
4. A patient is likely to require intensive care facilities and expertise when meningococcal disease presents with features of septicaemia.
5. Surgical ventricular drainage may be needed if obstructive hydrocephalus develops especially in tuberculosis meningitis.
6. Chemotherapy could be used in the treatment of bacterial meningitis e.g. meningitis caused by M. Tuberculosis can be treated with isoniazid or alternatively prednisolone.

Prevention and control

This is achieved via

1. Immunization
2. Personal and environmental control

Immunization

This has proven to be the most effective way in the prevention of meningitis. Immunizations against some organisms that cause meningitis include;

1. Routine vaccination with a new pneumococcal vaccine is recommended for children of 12yrs and below.
2. Breast feeding may protect children between 2- 5 months against meningitis caused by Haemophilus Influenzae.
3. Patients with cochlear implants should be vaccinated against streptococcus pneumoniae.
4. Haemophilus Influenzae type B vaccine: recommended for all children between 2months and 5yrs of age.
5. Measles, mumps and Rubella vaccine: this is routinely given to babies between 12 and 15months of age.
6. Varicella (chicken pox) vaccine: recommended for babies before the age of 18months and for the older children and adults who have not had chicken pox.
7. Men C vaccine: protects against group c meningococcal meningitis.
8. 7- Type conjugate vaccine: this is available for children as young as 2months against pneumococcal disease responsible for about 80% of cases of meningitis in children under 2months.
9. Neisseria meningitidis and streptococcus pneumoniae vaccines: recommended for patients who have medical conditions such as impaired immune system or people who have had meningitis in the past.
10. 23- Type polysaccharide vaccine: available to all those aged over 65 in Scotland, Northern Ireland and Republic of Ireland. Also available for those aged over 75 in England and Wales.

Personal and environmental control

1. Proper hygiene
2. All cases should be reported to the state or local health departments to assure follow up of close contacts and recognize outbreaks.
3. Separation of patients with meningitis from other normal people or individuals at home.
4. Avoiding insects and rodents that carry organisms that cause meningitis such as dogs, bats foxes etc.

Conclusion

   This endemic has been proven to be very fatal if left untreated because if diagnosed early and not treated can lead to complications and eventually death.

Despite the availability of bactericidal antibiotics with potent in vitro activity against the major meningeal pathogens, the morbidity and mortality rate from bacterial meningitis remain unacceptably high. Hence, care must be taken as individuals to play our own part in the prevention and control of this disease.