The clinical presentation of bacterial ME is slightly different from that of viral ME. Presentation of clinical signs and symptoms in both cases vary and are determined by patient's age, period of illness before presentation of the disease, and previous antibiotic therapy. Until the cause of ME becomes evident, the ME is termed as aseptic ME and is presented classically with meningeal symptoms, fever and CSF pleocytosis. 

Bacterial ME is characterized by fever, neck stiffness and altered level of consciousness. All the three symptoms are found to be present in 44% of patients while any two of them are observed in about 95% of infected individuals [9]. Altered mental status is typical of bacterial ME and occurs in about 66% of patients. Nuchal rigidity, Kernig sign, and Brudzinski sign might be absent  but the lack of these signs does not rule out the possibility of underlying ME [10]. The presence of lethargy is a common sign of bacterial ME and occurs specifically in pneumococcal meningitis. Development of coma and occurrence of seizures has been observed in about 20% of patients suffering from bacterial ME. 

The viral ME presents with extreme headache along with nausea, emesis, febrile illness and myalgias but the level of CNS consciousness is rarely altered unless the causative organism is herpes simplex virus. In children, the onset of viral ME is sometimes preceded by the presence of upper respiratory tract infection and otitis syndrome. If the ME is caused by group of enteroviruses and arboviruses, gastrointestinal upset may ensue and in same cases, diarrhea may also be present. Viral ME occurring from enteroviruses may result in rash, especially on hand, foot and mouth. Vascular instability is typically absent in viral ME. 

Identification of causative organism in ME is of utmost importance as the antimicrobial treatment is organism-specific. In order to establish accurate and specific diagnosis, all blood cultures must be acquired prior to administration of antibiotics. In about 50% of cases, the blood cultures are usually positive [11] [12].

Differentiation of bacterial ME from viral ME or aseptic ME can be achieved by measurement of levels of serum inflammatory markers. The causative organism is identified in blood cultures for bacterial ME in 70% of cases. Depending on the clinical presentation, neuroimaging is also performed along with blood cultures. Lumbar puncture demonstrates pressures more than 40 cm of H2O in comatose patients suffering from bacterial ME. Specific findings of bacterial ME are polymorphonuclear pleocytosis, hypoglycorrhachia and increased C-reaction protein concentrations. The elevated levels of procalcitonin above 5 2g/L in children and 2 2g/L in adults are also distinctive of severe bacterial ME.

In viral ME, concentrations of protein and glucose are mildly elevated with pronounced mononuclear pleocytosis but in the inital stage of infection, polymorphonuclear pleocytosis may be present in 40% of cases. In many cases of suspected viral ME, measurement of antibodies against specific viral antigens can aid in establishing diagnosis.  If ME is caused by herpes virus, polymerase chain reaction (PCR) may be used to establish diagnosis. 

Suspected case of bacterial ME must be treated as a medical emergency as slight delay in therapy leads to adverse prognostic outcomes. Strong suspicion of ME, presence of characteristic signs of the disease and recent history of close contact with a patient suffering from meningococcal infection requires urgent hospital admission.

Initiation of therapy requires restoration of patient's vital functions that include sustenance of blood pressure and treatment of septic shock. Patient must be monitored closely and empirical therapy should be initiated while awaiting results of diagnostic tests. Once diagnosis is established, treatment can be changed by using bactericidal antibiotic specific for the suspected organism. In the United States, the use of Vancomycin is recommended in treatment of bacterial ME [13].

The empirical therapy of suspected bacterial ME in immunocompetent individuals includes administration of Ampicillin and Cephalosporin or an Aminoglycoside in neonates. In infants, children and adults, a third generation Cephalosporin and Vancomycin may be used while in elderly patients, Ampicillin may be administered along with a third generation cephalosporin. In immunocompromised individuals, the preferred choice of antibiotics are Ampicillin and Ceftazidime. 

In cryptococcal ME, treatment includes initial therapy with administration of Amphotericin B in dosage of 0.7-1 mg/kg/day via IV route for 2 weeks, with inclusion of Flucytosine in dosage of 100mg/kg via oral route in 4 divided doses. For consolidation therapy, Fluconazole in dosage of 400 mg/day for 8 weeks or alternatively Itraconazole is administered. Maintenance therapy requires long term treatment with Fluconazole in dosage of 200 mg/day. This dosage is most effective in prevention of relapse.

Primary amebic meningoencephalitis (PAM), a fatal illness caused by Naegleria fowleri has been reported to be treated with high dose of Amphotericin B or Miconazole (via intravenous or intrathecal route) along with Rifampin.

Another form of ME known as helminthic eosinophilic ME is treated with supportive therapy of analgesia, CSF aspiration and administration of corticosteroids. Anthelmentic therapy is contraindicated in helminthic eosinophilic ME because death of helminths following administration of anthementics results in severe inflammatory reactions and death of the patient.

In community acquired ME, the recommended treatment is administration of Dexamethasone in dosage of 10 mg via IV route every 6 hours for 4 days. 

Despite the availability of potent antimicrobial therapy, the disease still possesses higher mortality and morbidity rates. Prompt diagnosis and initial management is imperative in developing positive outcome as delay in diagnosis results in morbidity and death.

As mentioned earlier, ME possesses both, bacterial and viral etiologies. Majority of the cases of ME are viral in origin with enteroviruses, the most common causative viral group for the disease; accounting for 60% of the cases . Other viruses that may be involved are neutrotropic viruses (herpesviruses and arboviruses).

In bacterial ME, the most common organisms involved are S. pneumoniae (pneumococcus) and N. meningitidis (meningococcus). The two bacteria account for more than 90% of ME cases in adolescents and young adults. Except for infants younger than 2 months of age, pneumococcus is responsible for more than 50% cases of bacterial ME [3]. Escherichia coli and Klebsiella species have been found to be responsible for one-third of nosocomial cases and only 3% of cases from the community.

Presence of certain predisposing disease conditions increases the risk of morbidity and mortality from ME. In 33% of cases, immunoglobulin deficiency, sickle cell disease, alcoholism or diabetes have been found to be present with ME [4].

The annual incidence rate (per 100.000) of bacterial ME is: 1.1 for S. pneumoniae, 0.6 for N. meningitidis, 0.3 for Group B steptococcus and 0.2 for both L. monocytogenes and H. influenza. The mortality rate of bacterial ME is approximately 9.4% for children and 20% in adults.

In bacterial ME, overcomes of host's immune response by bacterial virulence factor of pathogenic bacteria results in the development of infection as the bacterial virulence factor prevails over host defense mechanisms [5]. The pathogenetic mechanism behind ME is as follows.

After entering the host body, the bacteria attach themselves to nasopharyngeal epithelial cells where they colonize along the entire nasopharynx. The bacteria attach to the muscosal epithelial cells by secreting IgA proteases that damage the mucous barrier and interacting with host cell surface receptors that allow attachment to the nasophayrngeal epithelial cells. Once attached to the nasopharyngeal epithelial cells, the bacteria are carried to the intravascular space in membrane bound vacuoles. If the causative organism is H. influenzea, invasion occurs intracellularly by formation of separations in the apical junctions of columnar epithelial cells.

After entering the bloodstream, the bacteria remain encapsulated within protective polysaccharide coating which prevents them from being phagocytized by neutrophils. Through blood circulation, the bacteria then enter brain by adhering to the receptors present on choroid plexus and cerebral capillaries. This results in alteration of blood brain barrier (BBB) permeation and the bacteria ultimately enter brain through cerebrospinal fluid (CSF) [6]. Since the host defensive mechanism inside CSF is diminished due to inadequate concentrations of complement proteins, immunoglobulins, neutrophils, IgM, C3 and C4, the CSF becomes rapidly infected by the pathogenic bacteria [7]. Inside CSF, the bacterial cell induces inflammation inside and around meninges by stimulating the production of inflammatory mediators such as cytokines, interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF). The inflammatory mediators together alter various body functions by induction of meningeal inflammation.

In bacterial ME, altered BBB permeability and reduced resorption of CSF results in the development of vasogenic, cytotoxic and interestitial odema in the form of cerebral Edema. Cerebral Edema, along with the presence of increased CSF volume and cerebral blood volume, ultimately results in rise in intracranial pressure within 24-48 hours of hospitalization, one of the typical clinical presentations of bacterial ME [8].

ME can be prevented by chemoprophylaxis and immunoprophylaxis.

Antimicrobial chemoprophylaxis is recommended in medical and paramedical staff treating patients suffering from ME and in individuals closely associated with such patients. Suitable antibiotics for chemoprophylaxis must be administered within 24 hours of identification of the suspected case. Commonly used antibiotics for chemoprophylaxis are Rifampin, Ceftriaxone or Ciprofloxacin.

If the ME is caused by meningococci, polysaccharide vaccines are prescribed for immunoprophylaxis and are recommended in individuals who visit areas epidemic and hyperendemic with ME. The vaccine should be administered 10 days before departure.

Meningoencephalitis (ME) refers to the viral or bacterial infection of brain parenchyma, meninges and subarachnoid space which results in an inflammatory response by the CNS. ME possesses high morbidity and mortality rate if is not recognized promptly and managed accordingly. The disease leads to the development of life threatening CNS inflammatory response comprising coma, seizures, increased intracranial pressure and ischaemic infarcts [1].

ME can be either acute, subacute or chronic. In acute ME, the time to presentation of disease is typically hours to days, whereas chronic ME takes about 4 weeks to present characteristic symptoms. Management and treatment of ME depends on etiology and the time in which the clinical symptoms start to appear.

The disease possesses both, viral or bacterial causes. In acute bacterial ME, the affected age groups in majority of the cases are young or older adults. The causative organisms typically involved are Steptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, Group B steptococci and Haemophilus influenza. Viral ME, often called as Aspetic ME is caused by viruses and is the most common cause of ME in the United States [2]. Viral groups that have been recognized to be involved in the disease include enteroviruses, herpes viruses, arboviruses, HIV and rarely mumps. Aseptic ME syndrome refers to meningoencephalitis with non-bacterial origin and can either have viral or other etiologies. Causative organisms from ME other than bacteria and viruses include Parasites and Fungi. The parasitic organisms that may cause ME are Naegleria Fowleri, Acanthamoeba spp, Balamuthia spp, Strongyloides stercoralis, Taenia solium, whereas the common fungal species comprise Cryptococcus neoformans, Coccidiodis immitis, Candida spp, Aspergillus spp, and Blastomyces dermatitidis.

Meningoencephalitis (ME) is an infectious disease of brain caused by either bacteria, virus or other organisms. Viral ME is also referred to as aspetic ME but the term can be used for non-microbial ME as well. The disease causes inflammation of brain and the membranes surrounding brain and spinal cord. 

ME is a serious illness and requires prompt diagnosis and immediate treatment to achieve good clinical outcomes. Common characteristic symptoms of ME are fever, headache, nausea, vomiting, stiff neck and back, weak muscles, impaired judgement, confusion and drowsiness. The presence of seizures, loss of consciousness and sudden severe dementia indicate serious infection and require urgent hospital admission and emergency treatment. In infants suffering from ME, clinical presentation includes lack of appetite, fatigue, irritability and fever. ME is diagnosed by identification of specific microogranisms in blood cultures of patients suspected with the disease. 

In viral ME, suitable antiviral medications are prescribed while antibiotics are administered in bacterial ME. Along with antimicrobial treatments, other medications are used to control symptoms that ensue ME. These include treatment of seizures with anticonvulsants, reduction of brain swelling with corticosteroids, treatment of irritability and restlessness with sedative drugs and use of analgesics and antipyretics for headache and fever. 

It is possible to prevent ME to some extent by prophylactic use of antibiotics in individuals who are in close contact with patients suffering from ME (medical and paramedical staff, close family members). For oversees individuals traveling to areas where ME is common, use of vaccine is recommended 10 days prior to traveling. 

1. Madhusudan M. Acute bacterial meningitis. In: Radhakrishnan K. Reviews in Indian Neurology 2003. Trivandrum, Kerala, India, Sree Chitra Tirunal Institute For Medical Sciences and Technology; 2003:1-47.
2. Rotbart HA. Viral meningitis. Semin Neurol. 2000;20(3):277-292.
3. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States. N Engl J Med. 2011; 364(21):2016-2025.
4. Kastenbauer S, Pfister HW. Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain 2003;126(5):1015-1025.
5. Tripathi BK, Gupta B, Agrawal AK. Acute Meningitis. In: Agrawal AK, Singal RK, Jain DG, Upadhyay R, Rewari BB. Emergency Medicine. Jaypee Brothers. 2005;258-269.
6. Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med. 1992;327:864-872. 
7. Parkkinen J, Korhonen T. Binding sites in the rate brain for E. coli S fimbriae associated with neonatal meningitis. J Clin Invest. 1988;81:860-865.
8. Ashwal S, Tomasi L. Bacterial meningitis in children: pathophysiology and treatment. Neurology. 1992;42:739- 748
9. Van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004;351(18):1849-1859.
10. Thomas KE, Hasbun R, Jekel J, Quagliarello VJ. The diagnostic accuracy of Kernig’s sign, Brudzinski’s sign, and nuchal rigidity in adults with suspected meningitis. Clin Infect Dis. 2002;35(1):46-52.
11. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2001;108(5):1169-1174. 
12. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010;23(3):467-492.
13. Mc Master P, Mcintyre P, Gilmour R et al. The emergence of resistant Pnemmococcal Meningitis. Implication for Empiric therapy. Arch Dis Child. 2002;87:207-211.