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Sunday, 3 November 2013

Meningitis

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)

Signs and Symptoms
In the research posted in European Journal of Pediatrics, scientists showed that
1.  The most common symptoms according to age were as follows: 1–5 months: irritability (85%), 6–11 months and 12 months or more: vomiting (82%) and neck rigidity (78%).
2. Meningitis should be suspected in irritable or lethargic febrile children despite absence of neck rigidity. Fever and vomiting were the most frequent reasons for consulting a physician (60% and 31%, respectively). Despite the frequency and alarming character of irritability, impaired consciousness and neck rigidity, their presence led infrequently to a consultation (6%, 22% and 3%, respectively).(8)

2. In other study to identify 433 patients with viral meningitis and 101 TBM patients and compared their clinical and laboratory features. Multivariable analysis showed a statistically significant association between TBM and the following variables: duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures, mild focal signs, multiple cranial nerve palsies, dense hemiplegia or paraparesis), cerebrospinal fluid/blood glucose ratio < 0.5 and cerebrospinal fluid protein level > 100 mg/dl(10)

3. Confusion
Confusion is also associated with symptoms of meningitis. in study of a seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion(9)

4. Other symptoms include sleepiness, discomfort looking into bright lights and In some cases, rash may be presented as a result of meningococcal bacteria.

5. Etc.


Causes and risk factors
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)

5.4. Etc.

B. Risk factors
Some people are more susceptible to meningitis than others

1. People with weakened immune systems
In a study conducted by Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Dr. Koppe U and the research team indicated "The innate immune system is critical for the control of colonization and for defence during invasive disease. Initially, pneumococci are recognized by different sensors of the innate immune system called pattern recognition receptors (PRRs), which control most subsequent host defence pathways. These PRRs include the transmembrane Toll-like receptors (TLRs) as well as the cytosolic NOD-like receptors (NLRs) and DNA sensors". Streptococcus pneumoniae is both a frequent colonizer of the upper respiratory tract and a leading cause of life-threatening infections such as pneumonia, meningitis and sepsis.(21)

2. Pregnant women
In the examine listeriosis cases reported through the U.S. Listeria Initiative during 2004-2007. Cases were classified as pregnancy-associated if illness occurred in a pregnant woman or an infant aged <28 days. Of 758 reported Listeria cases, 128 (16.9%) were pregnancy-associated. Maternal infection resulted in four neonatal deaths and 26 (20.3%) fetal losses. Invasive illnesses in newborns (n=85) were meningitis (32.9%) and sepsis (36.5%)(21). There is a case report of TBM in a previously healthy woman whose signs and symptoms developed immediately after delivery and were initially attributed to postpartum depression and a puerperal-acquired bacterial infection.  Although tuberculous meningitis (TBM) rarely complicates pregnancy and seldom occurs in puerperal women,(22)

3. Chronic Diseases 
a. AIDS 
People with AIDS are more susceptible to develop Meningitis. In a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 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.(23)

b.  Diabetes
In a study conducted by , Far Eastern Memorial Hospital, Dr. Ho MP and the research team showed that advanced age, newly recognized DM, K. pneumoniae bacteremia, and DIC may be the cause of a fatal Klebsiella pneumoniae meningitis and concomitant disseminated intravascular coagulation (DIC) in a 72-year-old woman(24)

c. Rheumatoid arthritis
People with Rheumatoid arthritis may have an increased risk of Meningitis. Even though most common complications of RA occur in the severe and chronic stages of the disease, but Meningoencephalitis is a rare but aggressive complication of rheumatoid arthritis (RA).(25)

d. Others chronic diseases such as heart diseases, liver disease may also  risk factors of meningitis

4. Removal of your spleen puts you at risk for meningitis, as spleen is essential part of the immune system

5. In the study to overview outcome of meningococcal meningitis in Slovakia, researcher(s) indicated that risk factors such as underlying disease, cancer, diabetes, alcoholism, surgery (brain surgery), age (children under 5, teens and young adults ages 16 to 25 (especially college freshman living in dorms), and adults over 55), previous infections, trauma, sepsis were recorded and mortality, survival with sequellae, therapy failure were compared between meningococcal and non-meningococcal cases of bacterial meningitis(26)

f. Etc.
 

Complications and diseases associated
A. Complications
1. In the study to raise awareness of meningitis and its symptoms and describes some of the practical support that can be offered to sufferers, their families and friends. Doctors at the University of Hertfordshire. indicated that he prognosis and possible complications are described. These include potential problems such as sensorineural deafness, raised intracranial pressure, the need for skin grafting and the amputation of limbs and/or digits.(1)

2. Spectrum of complications 
Systematically central nervous system and systemic complications during the acute phase of adult bacterial meningitis
a. Central nervous system complications
Include brain swelling, hydrocephalus, brain abscess, subdural empyema, or subdural effusion (using computed tomography) and cerebrovascular involvement (using cerebral angiography),
b. Systemic complications
Include septic shock, disseminated intravascular coagulation, adult respiratory distress syndrome, or septic or reactive arthritis(30). Cerebrovascular complications are the most frequent intracranial complications in bacterial meningitis of the adult (37.1%) and are major determinants in the prognosis of this disease(31)

3. Others spectrum of complications

In the analysing 87 consecutive cases between 1984 and 2002. Meningitis-associated intracranial complications developed in 74.7% and systemic complications in 37.9% of cases. Diffuse brain oedema (28.7%) and hydrocephalus (16.1%) developed more frequently than previously reported. The incidences of arterial (21.8%) and venous (9.2%) cerebrovascular complications were also very high. Furthermore, 9.2% of cases developed spontaneous intracranial haemorrhages (two patients with subarachnoid and two with subarachnoid and intracerebral bleedings, all in association with vasculitis; one subject with intracerebral haemorrhage due to sinus thrombosis; and three cases with intracerebral bleedings of unknown aetiology). Other new findings were the incidence of acute spinal cord dysfunction due to myelitis (2.3%) and that of hearing loss (19.5% of all patients and 25.8% of survivors). The in-hospital mortality was 24.1%. Only 48.3% of the patients had a good outcome at discharge (32)

4. Etc.


B. Diseases associated
1. Hodgkin's disease
In a report of  a seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. and exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin's disease. The treatment of Hodgkin's disease led to perfect recovery of cognitive function.(9)

2. AIDS
Patient with AIDS are susceptible to
a. Cryptococcal
b. Tuberculous
c. Syphilitic
d. Listeria species
e. Lymphomatous
f. Aseptic
as a result of infections and very low CD4+ lymphocyte counts.(27)

3. Kikuchi's Disease
Kikuchi's disease is an idiopathic illness, typically causing cervical lymphadenopath. Dr. Dr. Mahdad Noursadeghi, Dept. of Infection & Tropical Medicine, Northwick Park Hospital in the study of "Kikuchi's Disease: A Rare Cause of Meningitis?" said that many patients with Kikuchi's disease who present with fever and meningitis will be assessed by infectious disease physicians who will not be aware of the association of Kikuchi's disease with meningitis.(28)

4. Other diseases
In the data collected from medical records of all adult patients with bacterial meningitis admitted to Chang Gung Memorial Hospital-Kaohsiung from January 1986 to December 2000, three of the 14 patients with ALD had liver cirrhosis (2 with Child's class B and 1 with Child's class C). The causative pathogens of these 14 cases were Klebsiella pneumoniae in 11, Staphylococcus aureus in 2 and Enterococcus in 1. Diabetes mellitus (DM) was the most common underlying disease and was present in 64% of patients (9/14). All patients with DM had K. pneumoniae as the causative pathogen. Bacteremia and thrombocytopenia were found in 64% (9/14) and 50% (7/14) of the patients, respectively. Focal suppurations including brain abscess, intracranial subdural empyema, and cervical epidural abscess were found in 4 patients. The overall mortality rate was 14% (2/14). ALD accounted for 11.5% (14/122) of the underlying conditions of all adult cases of community-acquired spontaneous bacterial meningitis treated during the study period.(29)

Diagnosis 
1. Spinal tap
After assessing the symptoms and taking the physical exam, the diagnosis is to obtain a sample of spinal fluid to identify type of bacteria responsible by performing a  lumbar puncture with local anesthetic and a needle inserted into an area in the lower back where fluid in the spinal canal, but the risk of lumbar puncture can lead to brain herniationis  if there is an elevation of a mass in the brain (tumor or abscess) or the intracranial pressure (ICP)(33).

2.  The Xpert EV test
Approved by the Food and Drug Administration (FDA) in 2007, when used in combination with other laboratory tests, will help physicians distinguish between viral meningitis and the less-common, but more severe, version of meningitis caused by detecting the RNA of the enterovirus that causes meningitis, but results from the Xpert EV test are available in two and one-half hours(34)

3. Meningococcal rash pressure test
Patient with rash and a cold or flu with fever, headache, aches and pains in joints and muscles and suspected to have menigitis, meningococcal rash pressure test may be the best choice. By using medical instruments to apply pressure to the skin around, bacterial meningitis will not whiten under pressure. As Meningococcus bacteria cause several different infections besides meningitis. They can cause different forms of blood poisoning: septicemia, which is severe; and meningococcemia, a milder form; also pneumonia, arthritis, and infections of the heart, eye, or other parts of the body(35)

4. Blood Culture Tests
Blood Culture Tests is to  is a microbiological culture of blood to detect for the presence of  of meningococcal bacteria.

5. Etc.

Preventions
A. Do's and Do not's list
1.  Behavioral
Neisseria meningitidis bacteria are spread through the exchange of respiratory and throat secretions like spit (e.g., living in close quarters, kissing). Fortunately, these bacteria are not as contagious as what causes the common cold or the flu. Also, the bacteria are not spread by casual contact or by simply breathing the air where a person with meningococcal disease has been(36). Especially when you are pregnant to avoid listeriosis

2. Eat your vegetable and fruits
Vegetable and fruit contain high amount of antioxidant, not only enhances the immune system but also fight against foreign virus and bacteria infection and inflammatory causes of meningitis(37)

3. Avoid excessive drinking
Excessive drinking can increase the risk of liver diseases that can lead to weaken immune function causes of meningitis


4. Moderate exercise
Moderate exercise can enhance the circulatory system and increase the function of immune system in fighting against bacterial and viral invasion.


5. Smoking
The odds ratio of purulent meningitis for children receiving passive smoking was 3.0, and the 95% confident limit was greater than 1 (P < 0.05). There was significant dose-effect relationship between the daily dosage of cigarette smoked by family members and the odds ratio of purulent meningitis (P < 0.005)(38)

6. Etc.

B. Diet against meningitis
1. Flaxseed oil is extracted from the seeds of the flax plant (Linum usitatissimum) contained both omega-3 and omega-6 fatty acids. Flaxseed oil generally contains 50% of the omega-3 fatty acid - alpha-linolenic acid and 25 % of the omega-6 fatty acid linolenic acid, 15 % of mainly monounsaturated oleic acid and trace amounts of palmitoleic acid and eicosenoic acid.
In the investigation of Omega 3 fatty acids and theirs effect on inflammation, a physiological response to tissue trauma or infection found that dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFAs, according to "Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment" by Tull SP, Yates CM, Maskrey BH, O'Donnell VB, Madden J, Grimble RF, Calder PC, Nash GB, Rainger GE.(46)

2. Green Tea
a. Antimicrobial activities
 In the investigation of Antimicrobial activities of green of the study of "Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus" by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N., researchers found that flavonoids in green tea has exerted its ability in protective effects against Bacillus cereus.(47)

b. Immune system
a. In the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK., researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(48)

3. Garlic
Garlic is the natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. Garlic cooked is fine but it loses many of its health-giving powers. Raw garlic does most of its antibiotic and preventive medicines. Here are some of effective use of garlics for PROVEN DISEASE CURED.

4. Blueberry
In the investigation of Blueberry and blackberry wines commercially available in Illinois and theirs potential health benefits, found that fruit wines made from blueberries and blackberries may have potential health applications and therefore could contribute to the economy of the wine industry. Practical Application: The majority of wines are produced from grapes, but wine can also be produced from other fruits including blueberries and blackberries, which contain phenolic compounds that may contribute to human health, according to "Comparison of Chemical Composition and Antioxidant Capacity of Commercially Available Blueberry and Blackberry Wines in Illinois" by Johnson MH, Gonzalez de Mejia E.(49)


5. Shiitake mushroom
a. Immune system
Shiitake mushroom enhances the immune system in fighting against infection and disease. influenza, viruses and irregular cells growth due to it anti-tumor polysaccharide lentinan, according to "Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers" by Yoshino S, Tabata T, Hazama S, Iizuka N, Yamamoto K, Hirayama M, Tangoku A, Oka M.(50)

b. Free radicals
Shiitake mushroom contains high levels of antioxidants such as L-ergothioneine, that helps to
reduce the risk of oxidative cause of mutation in cell division and alternation, according to"Ergothioneine; antioxidant potential, physiological function and role in disease" by Cheah IK, Halliwell B.(51)

6. Etc.

 
C. Nutritional supplement against meningitis
 1. Vitamin A, C, E. D.
a. a. Vitamin A
Vitamin A occurs in the form retinol and is best known for its function in maintaining the health of cell membrane, hair, skin, bone, teeth and eyes. It also plays an important role as an antioxidant as it scavenges free radicals in the lining of the mouth and lungs; prevents its depletion in fighting the increased free radicals activity by radiation; boosts immune system in controlling of free radicals; prevents oxidation of LDL and enhances the productions of insulin pancreas.

b. Vitamin C
Vitamin C beside plays an important role in formation and maintenance of body tissues, it as an antioxidant and water soluble vitamin, vitamin C can be easily carry in blood, operate in much of the part of body. By restoring vitamin E, it helps to fight against forming of free radicals. By enhancing the immune system, it promotes against the microbial and viral and irregular cell growth causes of infection and inflammation.
Vitamin C also is a scavenger in inhibiting pollution cause of oxidation.

c. Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols discovered by researchers Herbert Evans and Katherine Bishop. It beside is important in protecting muscle weakness, repair damage tissues, lower blood pressure and inducing blood clotting in healing wound, etc, it also is one of powerful antioxidant, by moving into the fatty medium to prevent lipid peroxidation, resulting in lessening the risk of chain reactions by curtailing them before they can starts.

d. Vitamin D
Reseacher found that vitamin D, a group of fat-soluble secosteroids is also a membrane antioxidant, with the ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol.(39)

2. Antioxidants
a. Catechin
a.1. Anti-inflammatory effect
In the preparation of the gel of Chinese medicine catechu, and to observe the release mechanism in vitro and anti-inflammatory activity in rats, found that the optimum condition of extraction from catechu was as follows, the concentration of ethanol, ratio of raw material to solvent, ultrasonic time, and extraction temperature were 50% , 1: 12, 35 min and 60 degrees C, respectively. The formulation of catechu gel was carbomer-9 400.5 g, glycerol 5.0 g, the extracts of catechu 50.0 mL, and triethanomine 0.5 mL The gel was semitransparent and stable. The drugs released quickly. The catechu gel reduced the paw edema considerably in dose-dependent manner compared to carrageenan-induced rat, according to "[Preparation and pharmacodynamics studies on anti-inflammatory effect of catechu gel].[Article in Chinese]" by Zheng X, Zheng C.(41)

a.2. Anti-influenza virus activity
In the study of Polyphenolic compounds present in green tea, particularly catechins, and its effect on strong anti-influenza activity, found that therapeutic administration of green tea by-products via feed or water supplement resulted in a dose-dependent significant antiviral effect in chickens, with a dose of 10 g/kg of feed being the most effective (P < 0.001), according to "Anti-influenza virus activity of green tea by-products in vitro and efficacy against influenza virus infection in chickens" by Lee HJ, Lee YN, Youn HN, Lee DH, Kwak JH, Seong BL, Lee JB, Park SY, Choi IS, Song CS.(42)

b. Quercetin
b.1. Anti-Inflammatory effects
According to the study of `Antioxidant and Anti-Inflammatory Activities of Quercetin 7-O-β-D-Glucopyranoside from the Leaves of Brasenia schreberi.`by Legault J, Perron T, Mshvildadze V, Girard-Lalancette K, Perron S, Laprise C, Sirois P, Pichette A. (Source from Laboratory for Analysis and Separation of Plant Species (LASEVE), Université du Québec à Chicoutimi , Chicoutimi, Québec, Canada.), posted in PubMed, researchers found that some flavonoids have been reported to possess beneficial effects in cardiovascular and chronic inflammatory diseases associated with overproduction of nitric oxide. Quercetin-7-O-β-D-glucopyranoside possesses anti-inflammatory activity, inhibiting expression of inducible nitric oxide synthase and release of nitric oxide by lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Quercetin-7-O-β-D-glucopyranoside also inhibited overexpression of cyclooxygenase-2 and granulocyte macrophage-colony-stimulating factor.

b.2.  Antimicrobial and cytotoxic activities
According to the study of `Antimicrobial and cytotoxic activities of leaves, twigs and stem bark of Scutia buxifolia Reissek.`by Boligon AA, Janovik V, Frohlich JK, Spader TB, Forbrig Froeder AL, Alves SH, Athayde ML. (Source from a Phytochemical Research Laboratory, Department of Industrial Pharmacy , Federal University of Santa Maria , Build 26, room 1115 , Santa Maria , CEP 97105-900 , Brazil.), posted in PubMed, researchers found that quercitrin, isoquercitrin and rutin were identified by HPLC and may be partially responsible for the antimicrobial activities observed. This study reports for the first time the antimicrobial and cytotoxic activities of S. buxifolia leaves, twigs and stem bark.

c. Lycopene
c.1. Anti Inflammation
According to the study of `Inhibitory mechanism of lycopene on cytokine expression in experimental pancreatitis.`by Kim H. (Source from Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, South Korea. kim626@yonsei.ac.kr), posted in PubMed, researchers found that in pancreatic acinar cells, which is mediated by the activation of NADPH oxidase. Lycopene functions as a very potent antioxidant to suppress the induction of inflammatory cytokines, in pancreatic acinar cells stimulated with cerulein. In this review, the possible beneficial effect of lycopene on experimental pancreatitis shall be discussed based on its antioxidant activity.

c.2. Antioxidants
In the study of `Comparison of lycopene and tomato effects on biomarkers of oxidative stress in vitamin E deficient rats` by Delphine Gitenay, Bernard Lyan, Mathieu Rambeau, Andrzej Mazur and Edmond Rock. (Source from European Journal of Nutrition Volume 46, Number 8, 468-475, DOI: 10.1007/s00394-007-0687-2), posted in springerprotocols.com, researchers found that Our study showed for the first time that tomatoes, containing or not containing lycopene, have a higher potential than lycopene to attenuate and or to reverse oxidative stress-related parameters in a mild oxidative stress context.

d. Theaflavin
d.1. Antioxidant effects
In the investigation of four main TF derivatives (theaflavin (TF(1)), theaflavin-3-gallate (TF(2)A), theaflavin-3'-gallate (TF(2)B), and theaflavin-3,3'-digallate (TF(3))) in scavenging reactive oxygen species (ROS) in vitro, their properties of inhibiting superoxide, singlet oxygen, hydrogen peroxide, and the hydroxyl radical, and their effects on hydroxyl radical-induced DNA oxidative damage, found that compared with (-)-epigallocatechin gallate (EGCG), TF derivatives were good antioxidants for scavenging ROS and preventing the hydroxyl radical-induced DNA damage in vitro. TF(3) was the most positive in scavenging hydrogen peroxide and hydroxyl radical, and TF(1) suppressed superoxide. Positive antioxidant capacities of TF(2)B on singlet oxygen, hydrogen peroxide, hydroxyl radical, and the hydroxyl radical-induced DNA damage in vitro were found, according to "Evaluation of the antioxidant effects of four main theaflavin derivatives through chemiluminescence and DNA damage analyses" by Wu YY, Li W, Xu Y, Jin EH, Tu YY.(43)

d.2. Antibacterial effects
in the evaluation of the antibacterial effects of various concentrations of theaflavin as well as combinations of theaflavin and epicatechin, using the disk diffusion assay, found that strong antibacterial activity of theaflavin against eight clinical isolates of S. maltophilia and A. baumannii. Significant synergy (P≤0.05) was also observed between theaflavin and epicatechin against all isolates, according to "Antibacterial effects of theaflavin and synergy with epicatechin against clinical isolates of Acinetobacter baumannii and Stenotrophomonas maltophilia" by Betts JW, Kelly SM, Haswell SJ.(44)

3. Minerals(40)
a. Manganese
Manganese is an essential trace nutrient in all forms of life. It is well known for its role in helping the body to maintain healthy skin and bone structure, but also acts as cofactors for a number of enzymes in higher organisms, where they are essential in detoxification of superoxide (O2−, with one unpaired electron) free radicals. Although superoxide is biologically quite toxic and is deployed by the immune system to kill invading microorganisms by utilizing the enzyme NADPH oxidase. Any Mutations in the gene coding for the NADPH oxidase cause an immunodeficiency syndrome.

b. Zinc
Zinc is an essential mineral that is naturally present in some foods. The ability of zinc in inhibiting oxidative processes has been recognized for many years. Chronic effects, zinc enhances the introduction of metallothioneins, which help to capture the superoxide and hydroxyl radicals due to cysteine residues, resulting in lessening the risk of oxidative stress. Over acute effects, zinc may reduce the postischemic injury to a variety of tissues and organs by involving the antagonism of copper reactivity as a result from its antioxidant functions.

c. Copper
Copper, an essential trace element is essential for the absorption and utilization of iron and distributed widely in the body and occurs in liver. Antimicrobial and viral Copper enhances the immune function in fighting against foreign invasion, such as bacteria and virus, thus reducing the risk of infection and inflammation by utilizing the absorption of oxygen and production of energy within cells.

4. Etc.


Treatments
A. In conventional Medicine
A.1. Vaccines
Vaccine is defined as is a biological preparation to enhance immune function against a particular disease.
1. Monovalent meningococcal C conjugate vaccine (MCV-C)
 One dose of serogroup C meningococcal conjugate vaccine (MCV-C) at 12 months of age is the most common immunization schedule in Canada, but immunity may wane over time.(52)

2. Tetravalent meningococcal polysaccharide vaccine (MPV-ACWY)
Serum bactericidal activity and antibodies against serogroups A and C were determined before and after they received MCV-C, and 4 weeks after they received MPV-ACWY. Near-total splenectomy provides a favourable immunological basis for natural and vaccine-induced protection against meningococcal serogroup A and C infections. Sequential meningococcal vaccination is immunogenic in patients splenectomized for hereditary spherocytosis.(53)

3. Meningococcal conjugate vaccine(MCV-4) 
A newly licensed vaccine (pneumococcal conjugate vaccine) that appears to be effective in infants for the prevention of pneumococcal infections and is routinely recommended for all children greater than 2 years of age.(54)

4. The pneumococcal polysaccharide vaccine
College freshman, especially those who live in dormitories are at higher risk for meningococcal disease and should be educated about the availability of a safe and effective vaccine which can decrease their risk. Although large epidemics of meningococcal meningitis do not occur in the United States, some countries experience large, periodic epidemics. Overseas travelers should check to see if meningococcal vaccine is recommended for their destination. Travelers should receive the vaccine at least 1 week before departure, if possible. Information on areas for which meningococcal vaccine is recommended can be obtained by calling the Centers for Disease Control and Prevention at (404)-332-4565. There are vaccines to prevent meningitis due to S. pneumoniae (also called pneumococcal meningitis) which can also prevent other forms of infection due to S. pneumoniae . The pneumococcal polysaccharide vaccine is recommended for all persons over 65 years of age and younger persons at least 2 years old with certain chronic medical problems(54)

5. Etc.

A. 2. Medication
1. Antibiotics
a. Bacterial meningitis can be treated with a number of effective antibiotics, depending to  the bacteria causing the infection, In the study of moxifloxacin and ampicillin + gentamicin in the treatment of Listeria monocytogenes meningitis in a rabbit meningitis model, scientists at Ege University showed that moxifloxacin (M), ampicillin + gentamicin (A), ampicillin + gentamicin 2 (A2) and control (C). Group M received 20 mg/kg moxifloxacin at the end of the incubation time and 5 h later by intravenous (i.v.) route. Group A received ampicillin (30 mg/kg/h) and gentamicin (2.5 mg/kg/h) by i.v. route with continuous infusion for 8 h in 36 mL of 0.9% NaCl, group A2 received the same dosage of gentamicin and ampicillin in two different 36 mL 0.9% NaCl solutions and group C did not receive any treatment. Cerebrospinal fluid (CSF) samples (0.1-0.25 mL) were obtained 16 and 24 h after induction of meningitis. When the three treatment groups were compared, bacterial counts were found to be similar (P > 0.05)(55)

b. Side effects are not limit to diarrhea and gastrointestinal discomfort. In some cases, antibiotics can cause
b.1. Vomiting Severe watery diarrhea and
b.2. Abdominal cramps
b.3. Allergic reaction, such as shortness of breath, hives, swelling, etc.
b.4. Skin  Rash
b.5. Etc.

2.  Corticosteroids
a. Dexamethasone treatment may be associated with a lower mortality in adults and fewer neurological and auditory sequelae in adults and children from high-income countries, in particular in adults suffering from pneumococcal meningitis. In contrast, studies conducted in developing countries have yielded less favourable results.(56). Others suggested that the adjunctive administration of corticosteroids is beneficial in the treatment of adolescents and adults with bacterial meningitis in patient populations similar to those seen in high-income countries and in areas with a low prevalence of HIV infection.(57)

b.  Side effects are not limit to
b.1. stomach irritation
b.2. rapid heartbeat (tachycardia)
b.3. nausea
b.4. insomnia
b.5. Etc.
Other severe side effects include hyperglycemia, insulin resistance, diabetes mellitus,osteoporosis, cataract, anxiety, depression, colitis, hypertension, ictus, erectile dysfunction, hypogonadism, hypothyroidism, amenorrhoea, and retinopathy.(58)

A.2. Viral Meningitis 
1. According to the statistic
Enteroviruses account for more than 85% of all cases of viral meningitis,  Arboviruses account for about 5% of cases in North America, Herpes family viruses (Herpes simplex virus (HSV)-1, HSV-2, varicella-zoster virus (VZV), Ebstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 collectively)  cause approximately 4% of cases of viral meningitis(58)

2.  There is no treatment for viral meningitis, as the immune system, however, will produce antibodies to destroy the virus. Care must be taken during the Leighton for the body to run its course.


A.3. Aseptic meningitis
Clinicians must consider partially-treated bacterial meningitis as a possible etiology for the aseptic nature of their patient's disease; for example, patients with bacterial otitis and sinusitis who have been taking antibiotics may present with meningitis and CSF findings identical to those of viral meningitis.(58)

A.4. Parasitic meningitis
Parasitic meningitis usually is treat with a benzimidazole derivative or corticosteroid
1. Benzimidazole derivative
a. Albendazole 
Researchers at the Chung Shan Medical University, in the study of the efficacy of Albendazole  in parasitic meningitis, showed that examination of brain tissue revealed a similar pattern of decrease (48.6% by day 7, and 53.9% by day 14). Albendazole may thus be an effective compound for the treatment of angiostrongyliasis through its larvicidal activity and facilitation of an improved inflammatory response via the reduction of MMP-9 activity(59)

b. Albendazole-GM6001 co therapy
The combination treatment reduced MMP-9 activity by 89.2% in cerebrospinal fluid. The numbers of inflammatory cells increased significantly upon establishment of infection, but subsided upon co-treatment. Significantly fewer larvae were recovered from treated mice than from untreated, infected mice. The present results strongly suggest that co-therapy with albendazole and GM6001 may be an useful approach for the treatment of human angiostrongyliasis.(60)

c. Etc.

2. Corticosteroid
Dr. Sawanyawisuth K, at the Khon Kaen University, in the study of Drug target in eosinophilic meningitis caused by Angiostrongylus cantonensis showed that eosinophilic meningitis caused by Angiostrongylus cantonensis is an emerging infectious disease. It is the most common form of human angiostrongyliasis. The diagnosis is made by clinical criteria including the presence of cerebrospinal fluid eosinophils and a history of exposure to A. cantonensis larvae, e.g., from raw freshwater snails or contaminated vegetables. Among various treatment options, corticosteroid is the only effective treatment.(61)

3. Others suggested treatment options consist of symptomatic interventions, steroid therapy, antihelminthic therapy, or a combination of these strategies(62). Others showed that interleukin-12 and mebendazole lower levels of worm recovery and dramatic lessening of the eosinophilic meningitis. A reverse transcriptase PCR assay of mRNA expression in the brain also revealed that the use of IL-12 had shifted the immune response of the mouse from Th2 type to Th1 type.(63)

4. Etc.

A.5. Non medication causes of meningitis
There is report of 39-year-old woman with systemic lupus who presented with recurrent aseptic meningitis secondary to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), clinical manifestation resolved rapidly with ibuprofen discontinuation, and corticosteroids therapy was unnecessary. Aseptic meningitis related to NSAIDs reported in lupus patients should be considered because of their specific modality of care and their favourable outcome.(64).

B. Treatment in herbal medicine(71)
The aim of  herbal remedies are to aid the recovery process during recover phase from meningitis by strengthening the body immune system.
1. Garlic
a. Antifungal antitumor cytotoxicity and blood coagulability effects
In the identification of organosulfur compounds and theirs effects on cardiovascular diseases found that in vitro antifungal antitumor cytotoxicity and blood coagulability effects of steroid saponins from garlic and related Allium species are provided. Animal studies on the cholesterol-lowering effects of the saponin fractions from garlic are also summarized, according to "Saponins in garlic as modifiers of the risk of cardiovascular disease" by .Matsuura H(67)

b. Antioxidant effects
In the study of the Extracts of aged fresh garlic that are aged over a prolonged period and its antioxidant effects found that the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease, according to "Antioxidant health effects of aged garlic extract" by
Borek C.(68)

2. Ginseng
a. Antioxidant activity
In the evaluation of the extraction conditions of polysaccharides from the rhizomes of Panax japonicus C.A. Meyer and its antioxidant effect found that antioxidant activity exhibited Panax japonicus polysaccharides (PJP) had a good potential for antioxidant, according to "Optimization of polysaccharides from Panax japonicus C.A. Meyer by RSM and its anti-oxidant activity" by Wang R, Chen P, Jia F, Tang J, Ma F.(69)

b.  Immunological activities
In the study of Water-soluble ginseng oligosaccharides (designated as WGOS) with a degree of polymerization ranging from 2 to 10 were obtained from warm-water extract of Panax ginseng roots, found that WGOS were potent B and T-cell stimulators and WGOS-1 has the highest immunostimulating effect on lymphocyte proliferation among those purified fractions. It is hoped that the WGOS will be developed into functional food or medicine, according to "Structural characterization and immunological activities of the water-soluble oligosaccharides isolated from the Panax ginseng roots" by Wan D, Jiao L, Yang H, Liu S.(70)

3. Astralgus 
 a. Immune system
Astragalus polysaccharides (APS) isolated from astragalus enhances the immune system by enhancing and regulating the function of T cells, by suppressing the CD4(+)CD25(+)Treg activity, at least in part, via binding TLR4 on Tregs and trigger a shift of Th2 to Th1, according to the study of "Astragalus polysaccharides attenuate postburn sepsis via inhibiting negative immunoregulation of CD4+ CD25(high) T cells" by Liu QY, Yao YM, Yu Y, Dong N, Sheng ZY., posted in PubMed(65)
C. Treatment in Traditional Chinese medicine

b. Anti-inflammation
Astragalus has exerted an anti-inflammatory effect as a result of inactivation the p38 and Erk1/2 and inhibition NFkappaB-mediated transcription, according to the study of "Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk" by Ryu M, Kim EH, Chun M, Kang S, Shim B, Yu YB, Jeong G, Lee JS., posted in PubMed(66)



C. In Chinese medicine(72)
C.1. Meningitis is defined as a condition caused by
1. Heat excess in the Liver channel stirring up internal movement of Wind. Liver-Yang rising
a. Symptoms
a.1.  High fever;
a.2.Irritability
a.3. Persistent fever
a.4. Restlessness
a.5. Loss of consciousness
a.6. Restless legs
a.7. Dry tongue with red-tipped spots;
a.8. Rapid-Wiry pulse
a.9. Etc.

b. Formula Ling Jiao Gou Teng Tang(72)
* Ling Yang Jiao (Cornu Antelopis, Antelope Horn) - 4.5g.  -soothes liver, eliminates wind, clear heat  *Gou Teng (Ramulus cum Uncis Uncariae, Gambir Vine Stem, Gambir) - 9g.  -restores relationship between fire and wood (pericardium and liver)
*Sang Ye (Folium Mori Albae, White Mulberry Leaf) - 6g.  -expel wind, clear lung and liver heat
*Ju Hua (Flos Chrysanthemi Morifolii, Chrysanthemum Flower) - 9g.  -expel wind, clear lung and liver heat
*Bai ShaoYao (Radix Paeoniae Lactiflorae, White Peony Root, Peony) - 9g.  -nourish yin and fluids, soothe liver, relax sinews
*Sheng Di Huang (Radix Rehmanniae Glutinosae, Chinese Foxglove Root, Rehmannia) - 15g.  -nourish yin and fluids, soothe liver, relax sinews
*Chuan Bei Mu (Bulbus Fritillariae Cirrhosae, Tendrilled Fritillaria Bulb, Fritillaria) - 12g.  -clear heat, transform phlegm
* Zhu Ru (Caulis Bambusae in Taeniis, Bamboo Shavings) - 15g.  -clear heat, transform phlegm
*Fu Shen (Sclerotium Poriae Cocos Pararadicis, Poria Spirit) - 9g.  -clears heat, relieves irritability, calms restlessness
*Gan Cao (Radix Glycyrrhizae Uralensis, Licorice Root) - 2.4g.  -harmonize other herbs within formula, nourish yin, relax sinews, relieve spasms


2. Heat entering the terminal Yin channel. Vigorous Heat generates Wind, which leads to internal movement of Liver Wind
a. Symptoms
a.1. Migraine
a.2. Muscle spasms in the extremities
a.3. Opisthotonos
a.4. Tetanus
a.5.Trismus
a.6. Scarlet red,
a.7. Stiff tongue
a.8. Rapid-Wiry pulse
a.9. Etc.

b. Formula Zhi Jing San
*Quan Xie (Buthus Martensi, Scorpion, Buthus)  -extinguish wind, relieve spasms, stop pain, relieve toxicity
*Wu Gong (Scolopendra Subspinipes, Centipede, Scolopendra)  -extinguish wind, relieve spasms, stop pain, relieve toxicity

3. Heat excess which leads to internal movement of Liver Wind (in children). Phlegm-Heat in the Lungs
a. Symptoms
a.1. High fever
a.2. Pneumonia
a.3. Tetanus
a.4. Body rigidity
a.5. Opisthotonos
a.6. Restlessness
a.7. Spasms
a.8. Stiff jaw
a.9. Etc.

b. Hu Po Bao Long Wan(74)
*Niu Huang (calculus bovis) 7.8%
*Tian Zhu Huang (Concretio Siliceae Bamusae) 7.8%
*Dan Nan Xing (Pulvus Ariseamatis Cum Felle Bolvis) 3.1%
*She Xiang (Secretio Moschus)0.6%
*Quan Xie  (Buthus Martensi) 4.7%
*Jiang Can (Bombyx Batryticatus) 15.3%
*Zhu Sha (Cinnabaris) 4.7%
*Hu Po (Succinun) 3.8%
*Xiong Huang (Realgar)1.6%
*Chi Fu Ling (Sclerotium Poriea Cocus) 15.5%

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