Suppurative Meningitis Yu Dan Department of Neurology West China Second University Hospital

conception CNS Pathogen Bacteria Virus Tuberculosis Fungus Parasite Spirochetal Pathogen CNS

Suppurative Meningitis Acute infection of central nervous system(CNS). 90% of cases occur in the age of 1mo-5yr. The inflammation of meninges caused by various bacteria. Common features in clinical practices include: fever, increased intracranial pressure, meningeal irritation.  One of the most potentially serious infections, associated with high mortality (about 10%) and morbidity.

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Acute Suppurative Meningitis Etiology: First 2 months of life: Group B Streptococcus, gram negative bacilli, S. pneumoniae, Neisseria meningitides, Haemophilus influenzae type b. and L. monocytogenes. Children 2 mo-12yr of age 1- S. pneumoniae 2- N. meningitides Alterations of host defense: Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella spp., and L. monocytogenes.

*There are 3 main bacterial meningeal pathogens: Haemophilus influenzae Neisseria meningitides Streptococcus pneumoniae *Incidence varies by region and age.

Haemophilus influenzae Small GN, pleomorphic, coccobacilli H. flu type B causes almost ALL invasive disease Nontypeable Hib can rarely cause meningitis. Incidence of Hib decreased by 97% after vaccine

 Occurs predominantly in infants 2mo to 2yr of age  Many cases are in winter  Higher incidence of subdural effusion

Neisseria meningitidis - GN diplococci - Serotypes A,B,C,Y, and W135 cause most invasive disease. - Virulence depends on: Capsular polysaccharide LPS(endotoxin) Pili IgA protease ompS gene

Occur in epidemics (type A,C), which is more common in spring, or sporadic all the year (type B,C,Y)

Meningococcus is the only bacterium that frequently causes a rash, which is probably the most important clue to the diagnosis of meningococcal meningitis. It usually begins as a diffuse erythematous maculopapular rash. As the rash evolves, petechiae and purpura appear primarily on the trunk and lower extremities.

Streptococcus pneumoniae * Small, non-motile GPC in pairs or chains. * 8 serotypes cause 90% of invasive disease. 1, 4, 6, 9, 14, 18, 19 & 23 * Virulence depends on capsular polysaccharides * Associated with CSF leak (skull fractures), asplenia, HIV, cochlear implants

 Young infants ( <1yr) are most susceptible population  Peak season: spring and winter  Easier to have subdural effusion and hydrocephalus  Easily have a protracted course and relapse

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Predisposing factors 免疫功能低下 Immature immunologic function 血脑屏障不完善 (BBB) Immature blood-brain-barrier 脑脊膜膨出、颅脑手术、颅底骨折等 Impaired blood-brain-barrier

Route of infection brain Hematogenous dissemination （上感、皮肤感染、腹泻） Adjacent tissue infections (中耳炎、乳突炎、鼻窦炎) brain Congenital malformations (脑脊髓膜膨出、皮毛窦、脑脊液鼻漏)

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Pathology of suppurative meningitis Purulent exudate of leptomeningitis inflammation（ inflammation of pia and arachnoid spaces) over the convexities of the cerebral cortex. This may result in the additional complications of arterial or venous thrombosis with infarction and hemorrhage

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Clinical manifestion

The symptoms and signs are not evident in neonates and infants younger than 3mo of age; and patients already received irregular antibiotic therapy. Sequela 后遗症

Nervous system examination Meningeal irritation Neck stiffness Kernig sign Brudzinski sign

Neck stiffness keep the child with supine position without pillow, flex his head, if resistance exists, it means the test is positive.

Kernig sign keep the child with supine position without pillow, flex the hip and knee joint at 90°C, elevate a leg, if the child raises his head or has painful expression, it indicates the test is positive.

Brudzinski sign keep the child with supine position without pillow, flex the head, if the child flexes his legs involuntary at the same time, it means the test is positive.

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Diagnosis Step One: Meningitis, Yes or Not？ Step Two: Meningitis, Which type?

Attention Making Diagnosis As Early As Possible Noticing Atypical Case

Lumbar puncture

Contraindications of Lumbar puncture Severe intracranial hypertension Circulatory failure Infection of the puncture site If there is evident hemorrhage tendency

Normal CSF appearance

Diagnosis is confirmed by analysis of cerebrospinal fluid ( CSF)  Suggestion bacterial meningitis Increased pressure (90%) Appearance: slightly cloudy to purulent Raised white blood cells, consisting chiefly of polymorphonuclear leukocytes Raised protein concentration, decreased glucose concentration (80%)

Cerebrospinal fluid in neurologic infection Disease Pressure (Kpa) Aspect Total WBC (x106/L) Protein (g/L) Glucose (mmol/L) Smears Cultures normal 0.69-1.96 (0.29-0.78) clear 0-5 (0-20) 0.2-0.4 (0.2-1.2) 2.2-4.4 - Purulent meningitis  cloudy  (PMN) (1-5)  (<2.2) Gram’s stain + + Tuberculous Normal or cloudy (MN)  AFB stain +  Viral meningitis/ encephalitis Normal or  Normal (<1) Fungal meningitis India ink prep +

Other examination CT/MRI Indication ： Signs of abnormal localization Treatment is not satisfied Persistent fever Head circumference increased Significantly increased of intracranial pressure EEG Blood Tests, Blood cultures and Chest X-ray

Diagnosis Earlier diagnosis and prompt initiation of effective antibiotic treatment is critical for minimizing sequelae of purulent meningitis.  Suspected cases: febrile infants with seizure, meningeal irritability, increased intracranial pressure, altered mental status  Pay attention to the atypical symptoms and signs in neonate, infant and patient already received irregular antibiotic therapy

Differential Diagnosis Viral meningitis or encephalitis Febrile Seizure Toxic encephalopathy

Viral meningitis or encephalitis

MRI scans used in the diagnosis of herpes simplex virus (HSV). MRI typically shows temporal lobe lesions

Treatment Generally, management of viral encephalitis is nonspecific. Mild case : only symptomatic relief,e.g. fever, headache, vomiting. Severe case: Require hospitalization and intensive care.

Diagnosis of viral encephalitis Diagnosis of VE can be confirmed only by finding virus from the brain specimen, but it is carried out only in dead patients. Diagnosis of VE is relatively confirmed on the clinical presentations ,epidemiologic data, examination of CSF, findings of EEG, and neuroimaging studies.

Febrile Seizure Definition Febrile Seizures are the seizures with fever occurring in children between 6 months to 6 years of age without evidence of intracranial infection or defined cause

Febrile Seizure Associated with a rapidly rising temperature (usually develop when the temperature reaches 390C or greater ) Occur with the diseases out side the CNS Age dependent: 6mon-6year With normal CNS structure and function No no-febrile seizure history Genetic predisposition

Treatment Routine treatment: Search for the cause of fever Control fever (avoid excessive clothing, encourage fluids, tepid sponge bath, and antipyretics) Tepid 微温的

What to do in emergency Maintain clear airway Roll the child on to one side / prone with head lowered Diazepam 0.3-0.5 mg/kg I.V. Slowly in 2-3 Minutes May be repeated after 5 Minutes Rectal Diazepam (0.5 mg /kg)

Toxic encephalopathy Seen in severe systemic infection Can be high fever, delirium, unconsciousness, convulsions and coma CSF pressure increased while cytological and biochemical tests normal Bacillary dysentery

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication stimuli provoke convulsions with opisthotonos

Treatment 1- Initial Antibiotic Therapy: Early treatment Antibiotics susceptible to pathogens and with high permeability through BBB Given intravenously Enough dose Enough course of antibiotic therapy

Antibiotic therapy of bacterial meningitis Etiology Standard antibiotics of choice Duration of therapy H.influenzae Cefotaxime /Ceftriaxone 7-10days N.meningitidis 7days S.pneumoniae 2-3weeks Staphlococcus aureus Semisynthetic penicillins (Oxacillin sodium, Cloxacillin sodium),Norvancomycin >3weeks E.coli (or + ampicillin) > 3weeks Unknown Cefotaxime/Ceftriaxone + ampicillin >2-3weeks

2-Supportive and symptomatic therapy Good evaluation and monitoring are essential Correction of dehydration and electrolyte disturbances and proper nutrition Management of neurological complications

3-Reduce intracranial pressure Osmotic therapy: intravenous mannitol 0.5-1g/kg/every time, q4-6h Combination with intravenous dexamethasone: 0.3-0.5mg/kg/day Endotracheal intubation and hyperventilation

4-Control seizures Diazepam: 0.3-0.5mg/kg iv (slowly) 0.5-0.75mg/kg (Enteroclysis) Phenobarbital: Load dosage: 15-20mg/kg IV Maintenance dosage: 3-5mg/kg.d IV

 Ventriculitis : lateral ventricle puncture and Treatment 5-Others  Ventriculitis : lateral ventricle puncture and injection of antibiotics locally  Epilepsy: AEDs

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication

Complication Subdural effusion and empyema Hydrocephalus Brain abscess Ventriculitis Deaf and motor disabilities

Other Complication Deafness Blindness Epilepsy Paralysis Mental retardation Behavioral problems

Subdural effusion and empyema

 No response to a sensitive antibiotic therapy Indications:  No response to a sensitive antibiotic therapy  Prolonged fever or fever reoccurring after an afebrile interval with effective treatment  Bulging fontanel, widening of sutures, enlarging head circumference, emesis, seizure, altered consciousness.  Improved CSF profile with more serious clinical manifestations

.Hydrocephalus Note the marked dilation of the cerebral ventricles. Hydrocephalus can be due to lack of absorption of CSF or due to an obstruction to flow of CSF.

Brain abscess

Prognosis The outcome of suppurative meningitis depends on the following factors: Natures of bacteria, and severity of the initial disease Age of the patient Whether the diagnosis made is earlier or not Patient’s response to the treatment, and whether the treatment is adequate or not. Any complications

Most patients make a full recovery from meningitis Most patients make a full recovery from meningitis. A small number of infected people end up with hearing or vision loss or brain damage. Vaccinations against some forms of meningitis are available. They are recommended for children under age 5, people in close contact with someone who has developed meningitis, college students, and people travelling to certain overseas destinations

Suppurative Meningitis Etiology Predisposing factors Pathology Clinical manifestation Diagnosis and Differential Diagnosis Treatment Complication Cephalosporin

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