Friday 29 November 2013

Meningitis - The Causes

Meningitis is defined as a condition of inflammation of the protective membranes,  covering the brain and spinal cord (meninges). Meningitis, a life threaten disease, can kill and immediate action can and does save lives.(1) Although bacterial meningitis has become an uncommon disease in the developed world. Unfortunately, because of limited economic resources and poor living conditions, many developing countries are still affected by the devastating consequences of this life-threatening systemic infection(2)

A. Causes
1. Bacterial
Bacterial causes of meningitis can be classified according to age group
a. In Infants and children In the report of "Acute bacterial meningitis in infants and children" conducted by Johns Hopkins University School of Medicine, scientists showed that bacterial meningitis continues to be an important cause of mortality and morbidity in neonates and children throughout the world. The introduction of the protein conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has changed the epidemiology of bacterial meningitis(12). Another study of "Meningitis in children in Fiji" showed that Over a 3-year period, all eligible children with suspected meningitis admitted to CWMH had blood drawn for culture. Of these children, those for whom is was possible were tested for a four-fold rise in antibody titers to Haemophilus influenzae type b (Hib) and pneumococcal surface adhesin A (PsaA). Cerebrospinal fluid (CSF) was taken for bacteriological culture and antigen testing. CSF was also tested by PCR for Streptococcus species, Neisseria meningitidis, Hib, Mycobacterium tuberculosis, and enterovirus.(13)
Some researchers suggested bacterial meningitis in young children can impair vestibular function completely, leading to delayed posturomotor development if meningitis occurs before independent walking, even in absence of neurologic impairment(11) 

b. In adult
 In adults, according to Community-Acquired Bacterial Meningitis in Adults, bacterial meningitis has an annual incidence of 4 to 6 cases per 100,000 adults (defined as patients older than 16 years of age), and Streptococcus pneumoniae and Neisseria meningitidis are responsible for 80 percent of all cases.(14). In a report conducted by National Institute of Infectious and Tropical Diseases, S. suis was commonly diagnosed as a cause of bacterial meningitis in adults in northern Viet Nam. In countries where there is intense and widespread exposure of humans to pigs, S. suis can be an important human pathogen.(15)


2. Viral
Certain virus can cause meningitis. Enteroviruses is defined as condition in which a virus that enters the body through the gastrointestinal tract and thrives there, often moving on to attack the nervous system.  are the most common cause at all ages, including 29 Coxsackieviruses (23 Coxsackie A viruses and 6 Coxsackie B viruses), 28 echoviruses, and 4 other enteroviruses.(16)
a. Varicella zoster virus 
Varicella zoster virus is defined as a condition of infection and results from exposure of a person susceptible to the virus. The virus remains latent in cranial nerve ganglia and reactivates and can cause a wide range of neurologic disease if a infected patient is association with a decline in cell-mediated immunity in the elderly and immuno-compromised. there are report of a 46-year-old female who initially presented with worsening headache, nuchal rigidity, fever, and a skin rash, who was subsequently found to have varicella zoster meningitis.(3)

b. Immunodeficiency virus and tuberculosis
In the study of 642 individuals conducted by University of KwaZulu-Natal, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis(4)

3. Aseptic meningitis
Aseptic meningitis is defined as a condition of all cases of meningitis in which no bacterial infection can be found. In the study of DIFFICULT AND RECURRENT MENINGITIS by L Ginsberg showed that examination yields a typical ‘‘aseptic meningitis’’ picture (elevated white cell count, predominantly lymphocytic, no organisms on Gram stain, normal or elevated protein concentration, normal or reduced glucose concentration) because of the breadth of the differential diagnosis, both infective and non-infective (table 1). In these circumstances, it is particularly important to exclude or diagnose tuberculosis, cryptococcosis, and other fungal infections, partially treated pyogenic meningitis, neurosyphilis, and Lyme disease, because of the need for urgent treatment and the consequences of failure to treat.(17)

4. Parasitic
It is a very common in underdeveloped countries as result of  parasites found in contaminated water, food, and soil, including Angiostrongylus cantonensis, Gnathostoma spinigerum, Schistosoma etc.

5. Non-infectious
5. 1. Medication
Meningitis is either caused by infection of bacteria or viral, but certain medication, including nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, intravenous immunoglobulins, and OKT3 antibodies (monoclonal antibodies against the T3 receptor) are the most frequent cause of Drug-induced aseptic meningitis (DIAM), as resolution occurs several days after drug discontinuation and the clinical and cerebrospinal fluid profile (neutrophilic pleocytosis) do not allow DIAM to be distinguished from infectious meningitis(7)

a. Infliximab
There are report of  a 51-year-old female, was being treated for Crohn's disease. After an infliximab infusion, she had headache, fever, arthralgia, myalgia, and meningismus. Infliximab commonly causes headache and is very immunogenic, we infer that infliximab-induced meningitis is immune-mediated and underrecognized. Potential risk factors and means for minimizing its occurrence are offered(4)


b. Spinal analgesia and anaesthesia
Even though spinal analgesia and anaesthesia (SA) is a rare predisposing condition to bacterial meningitis but, due to the seriousness of the infection, it should be considered in the differential diagnosis for any patient who develops fever or headache in this setting(5). Also there are report of two cases of meningitis which developed after combined spinal-extradural procedures for obstetric analgesia. The first case was thought to be caused by aseptic or chemical meningitis and the second was a case of bacterial meningitis in a patient who also received an extradural blood patch.(6)

5.2. Inflammatory conditions
a. Systemic lupus erythematosus
is defined as a condition of autoimmune diseases, as the immune system attacks the body's cells and tissue,of that lead to inflammation and tissue damage. There is report that Aseptic meningitis appears to be an early manifestation of SLE and may herald more serious brain damage. No new cases of aseptic meningitis occurred in this series after initiation of therapy for SLE. In contrast, bacterial meningitis did occur as a late complication of the disease(18)

b. Vasculitis
Vasculitis is defined as a inflammatory condition of the blood vessels as a result of group of diseases. In a study of a 53-year-old man with pneumococcal meningitis who developed numerous ischemic lesions in the brainstem and basal ganglia caused by parainfectious vasculitis, researchers suggested that parainfectious vasculitis may respond to late corticosteroid treatment. MMP-9 level in CSF may be a marker of vasculitic complication in bacterial meningitis.(19)

c. Migraine
Dr. Bruce H. Dobkin at the Daniel Freeman Hospital Medical Center Stroke/Neurological Rehabilitation Unit, wrote" Schraeder and Burns (ARCHIVES 1980;37:377-379) suggested that the rare CSF lymphocytosis found in patients with hemiplegic migraine results from a secondary meningeal reaction. Another report concluded that the complicated migraines of seven patients resulted from an inflammatory disturbance.....(20)

d. Etc.

5.3. Immunodeficiency virus and tuberculosis
In the study of 642 individuals conducted by University of KwaZulu-Natal, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis(4)

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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/15284663
(2) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2803%2913693-8/fulltext
(3) http://www.ncbi.nlm.nih.gov/pubmed/19918571
(4) http://www.ncbi.nlm.nih.gov/pubmed/22216407
(5) http://www.ncbi.nlm.nih.gov/pubmed/21093704
(6) http://www.ncbi.nlm.nih.gov/pubmed/7999501
(7) http://archinte.ama-assn.org/cgi/reprint/159/11/1185.pdf
(8) http://www.springerlink.com/content/t0130132486t8623/
(9) http://www.ncbi.nlm.nih.gov/pubmed/18930300
(10) http://www.ncbi.nlm.nih.gov/pubmed/22507645
(11) http://www.ncbi.nlm.nih.gov/pubmed/22445260
(12) http://www.ncbi.nlm.nih.gov/pubmed/20129147
(13) http://www.ncbi.nlm.nih.gov/pubmed/22342257
(14) http://www.nejm.org/doi/full/10.1056/NEJMra052116
(15) http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0005973
(16) http://www.medterms.com/script/main/art.asp?articlekey=11339
(17) http://jnnp.bmj.com/content/75/suppl_1/i16.full.pdf
(18) http://onlinelibrary.wiley.com/doi/10.1002/art.1780180414/abstract
(19) http://www.ncbi.nlm.nih.gov/pubmed/16757830
(20) http://archneur.ama-assn.org/cgi/content/summary/38/1/69

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