Purulent meningitis (PPM) remains one of the diseases with high morbidity and mortality worldwide. The epidemiology varies from country to country and region to region. The incidence rate in the United States is 3/(100,000*year). The incidence is higher in developing countries and may be related to lack of vaccination. It is an inflammatory disease of the cerebrospinal meninges caused by a purulent bacterial infection and is a common septic infection of the central nervous system. It usually has an acute onset and occurs in infants and children and in elderly people over 60 years of age. Tian Peichao, Department of Pediatric Internal Medicine, First Affiliated Hospital of Zhengzhou University
Disease classification
The incubation period of the disease is 1-7 days, usually 2-3 days. Clinically, the disease is classified into three types according to the condition and performance.
Common type
It accounts for 90% of cases. In 70% of cases, dark or purplish-red petechiae and petechiae of different sizes and uneven distribution appear on the skin and mucous membranes, and enter the meningitis phase after 1 to 2 days, with intracranial hypertension, manifested by increased headache, frequent vomiting (in the form of jets) and meningeal irritation signs (i.e., neck tonicity, angular reverberation grams, and Buerger’s sign). Toxicological manifestations such as body pain, irritability and dull expression, and in severe cases, lookout and coma. In infants and young children (under 2 years old), the symptoms of meningitis are often atypical because the skull suture and fontanelle are not closed, manifesting as high fever, vomiting, refusal to eat, crying and restlessness, and even convulsions, although there are no signs of meningeal irritation, but the fontanelle is full to help diagnose.
Fulminant fever
This type is mostly seen in children, the disease is fierce, if not rescued in time can die within 24 hours. Patients with brain parenchymal damage quickly enter coma, with frequent convulsions, hemiplegia, high blood pressure, dilated pupils on one side, loss of light reflex, eye fixation, and soon respiratory failure and death. This type is also divided into fulminant shock type and fulminant encephalitis type. In addition to the common symptoms of shock type, its prominent manifestation is the symptoms of systemic toxicity, extreme mental atrophy, pale face, cold limbs, skin pattern, reduced urine volume, decreased blood pressure, cerebrospinal fluid more clarified, cell count slightly increased or normal. Blood culture and bruise spot smear are positive. In the fulminant encephalitis type, the prominent manifestations are severe headache, irritability, frequent vomiting, convulsions, rapid coma, and eventually brain herniation and respiratory failure. Those with symptoms of both shock and encephalitis are mixed, and the death rate is extremely high.
Mild type
Only hemorrhagic spots on the skin and mucous membranes are present, and smear staining can reveal pathogenic bacteria; this type is mostly seen in children. [1]
Pathogenesis
The most common causative agents of pyogenic meningitis are pneumococcus, diplococcus meningitidis and Haemophilus influenzae type B, followed by Staphylococcus aureus, Streptococcus, Escherichia coli, Bacillus degeneratum, Anaerobes, Salmonella and Pseudomonas aeruginosa. [2]
Pathogenesis and pathophysiology
The source of infection can be caused by infection of the heart, lungs, and other organs spreading to the ventricles and subarachnoid system, or by direct spread of infected lesions in the skull, vertebrae, or brain parenchyma, or, in some cases, through cranial, sinus, or mastoid fractures or neurosurgical invasion of the subarachnoid space.
The pathological changes of septic meningitis caused by different pathogenic bacteria are basically the same. After the pathogenic bacteria invade the subarachnoid space via blood circulation, the bacteria multiply due to the lack of effective immune defense in the cerebrospinal fluid, and the antigenic components of the bacterial wall and certain cytokines mediating the inflammatory response stimulate the vascular endothelial cells, prompting neutrophils to enter the central nervous system and inducing a series of inflammatory pathological changes in the soft meninges.
1) The soft meninges and superficial vasculature of the brain become dilated and congested, and a large amount of purulent exudate from the subarachnoid space covers the surface of the brain and is deposited in the cerebral sulcus and the basal pool of the brain.
2) The color of purulent exudate is related to the type of pathogenic bacteria, with S. meningitidis and S. aureus being grayish-yellow, Streptococcus pneumoniae being light green, Haemophilus influenzae being gray, and P. aeruginosa being grass green.
3) When purulent exudate obstructs the arachnoid granules or brain pools, affecting the absorption and circulation of cerebrospinal fluid, it causes traffic or obstructive hydrocephalus.
4) Microscopically, a large number of polymorphonuclear granulocytes and fibrin exudates can be seen in the subarachnoid space, and pathogenic bacteria can be found both inside and outside the cells after Gram staining. The cerebral cortex adjacent to the soft meninges is mildly edematous, and in severe cases, it is complicated by arteritis, phlebitis, or thrombosis.
Clinical manifestations
The clinical manifestations of septic meningitis caused by various bacterial infections are similar and are mainly as follows.
Symptoms of infection
Fever, chills, or manifestations of upper respiratory tract infection, etc.
Meningeal irritation signs
Manifestation is cervical tonicity, positive Kernig’s sign and Brudzinski’s sign. However, meningeal irritation signs are often not obvious in neonates, elderly or comatose patients.
Increased intracranial pressure
It is manifested by severe headache, vomiting, and impaired consciousness. Intracranial pressure is significantly elevated when detected by lumbar puncture, and in some cases, brain herniation is even formed clinically.
Focal symptoms
Some patients may show symptoms of focal neurological impairment, such as hemiparesis and aphasia.
Other symptoms
Some patients have more specific clinical features, such as the rash that appears during meningococcal meningitis (also known as epidemic meningomyelitis) bacteremia, which starts as a diffuse red maculopapular rash and rapidly turns into cutaneous petechiae, mainly on the trunk, lower extremities, mucous membranes, and conjunctiva, and occasionally on the palms of the hands and soles of the feet.
Diagnosis and Differential Diagnosis
Diagnosis
The disease should be considered based on acute onset of fever, headache, vomiting, meningeal irritation on examination, elevated cerebrospinal fluid pressure, and markedly elevated white blood cells. Confirmation of the diagnosis requires pathogenic evidence, including the detection of pathogenic bacteria in the bacterial smear of cerebrospinal fluid and positive blood bacterial culture.
1) Routine laboratory tests
a) Routine blood tests: significant increase in total white blood cells and neutrophils. Anemia is commonly seen in H. influenzae meningitis.
b) Blood culture: Positive results can be obtained in early stage, without antibiotic treatment. It can help to identify the pathogenic bacteria.
c) Pharyngeal swab culture: isolation of pathogenic bacteria is of reference value.
d) Petechiae smear: The positive rate of bacteria detected in skin petechiae smear of children with rheumatoid encephalitis can be more than 50%.
2) Cerebrospinal fluid examination.
a) Routine: typical septic changes are seen. The cerebrospinal fluid is cloudy or thin rice-like in appearance, with increased pressure. Microscopic examination of leukocytes is very high and can reach hundreds of millions/L.
b) Biochemistry: Sugar quantification not only helps to identify bacterial or viral infections, but also reflects the effectiveness of treatment. The qualitative protein test is mostly strong positive, and the quantification is above 1g/L each.
c) Bacteriological examination: the cerebrospinal fluid is centrifuged and precipitated for smear staining, which can often detect pathogenic bacteria and can be used as a basis for early antibiotic treatment.
d) Immunological examination.
i. Convective immunoelectrophoresis (coumter-immunoec trophoresis, CIE): This method uses known antibodies (specific antisera) to detect antigens (such as soluble podoconjugates.) in the cerebrospinal fluid. It has high specificity and is often used for rapid diagnosis of rheumatoid brain, and also for the detection of H. influenzae and Streptococcus pneumoniae, with a positive rate of 70% to 80%.
ii. The results for S. meningitidis and S. influenzae are similar to those measured by the CIE method. However, the sensitivity to Streptococcus pneumoniae is poor. This method is more sensitive than CIE, but there is a possibility of false positives.
iii. The known antibodies are labeled with fluorescein, then the antigen to be tested (e.g. cerebrospinal fluid, blood specimen) is added, and then the antigen-antibody reaction is observed by fluorescence microscopy. This method has high specificity and sensitivity, and can make a rapid diagnosis, but requires certain equipment.
iv. Enzyme-linked immunosorbent assay.
e) Horseshoe crab spider lysate test : (1) The amount of immunoglobulin in normal cerebrospinal fluid is very low and IgM is lacking. In children with chemoencephalitis, IgM is significantly higher, such as greater than 30 mg/L, which basically excludes viral infection. (2) Normal cerebrospinal fluid LDH mean value: 53.1 IU in newborn; 32.6 IU in lactation; 29.2 IU in toddler; 28.8 IU in school age. normal LDH isoenzyme value; 127% LDH in newborn, 235% LDH,334% LDH, 243% LDH, 51% LDH. After 1 month of life, LDH137%, LDH232%, LDH328%, LDH42%, LDH51%. LDH values were significantly higher in children with chemoencephalopathy, and LDH4 and LDH5 in isoenzymes were significantly higher.
3) Imaging examination
The diagnostic and differential diagnostic significance of imaging examinations is limited. Some patients show enhanced signal in the meninges and cerebral cortex after enhancement, but the absence of enhancement does not exclude the diagnosis. The real significance of imaging is to understand the central nervous system complications of meningitis, such as brain abscess, cerebral infarction, hydrocephalus. Subdural pus accumulation and venous sinus thrombosis.
Differential diagnosis
1) Viral meningitis Cerebrospinal fluid leukocyte count is usually less than 1000×10∧6/ L, sugar and chloride are usually normal or slightly low, and bacterial smear or bacterial culture result is negative.
2) Tuberculous meningitis Usually subacute onset, cerebral nerve damage is common, and elevated cerebrospinal fluid count is often less pronounced than in septic meningitis.
3) Cryptococcal meningitis usually has an insidious onset and a prolonged course, and cerebral nerve involvement, especially optic nerve involvement, is common.
Treatment
Antibacterial treatment
The principle that should be mastered is early use of antibiotics, usually broad-spectrum antibiotics until the pathogenic bacteria are identified, and antibiotics should be selected if the pathogenic bacteria are clearly identified.
a) Undetermined pathogens: Ceftriaxone or cefotaxime of three generations of cephalosporins are often used as the first choice for septic meningitis and are more effective in septic meningitis caused by meningococci, pneumococci, Haemophilus influenzae and Streptococcus b.
b) Determining the pathogenic bacteria: Sensitive antibiotics should be selected according to the pathogenic bacteria.
i. Pneumococci: Those who are sensitive to penicillin can be treated with high-dose penicillin, 20-24 million U per day for adults and 400,000 U/kg per day for children, divided into intravenous drips. For those who are resistant to penicillin, ceftriaxone may be considered, combined with vancomycin if necessary. 2 weeks is a course of treatment, and cerebrospinal fluid is usually reviewed within 24 to 36 hours after starting antibiotic therapy to evaluate the effect of treatment.
ii. Meningococci: Penicillin is preferred, and cefotaxime or ceftriaxone is selected for drug resistance, and may be combined with ampicillin or chloramphenicol. Chloramphenicol is available for those who are allergic to penicillin or β-lactam antibiotics.
Gram-negative bacilli: Ceftazidime can be used for meningitis caused by Pseudomonas aeruginosa, and ceftriaxone, cefotaxime or ceftazidime can be used for meningitis of other gram-negative bacilli, often for a course of 3 weeks.
Hormone therapy
Hormones can inhibit the release of inflammatory cytokines and stabilize the blood-brain barrier. They can be considered for patients with severe disease and no obvious contraindications to hormones. Dexamethasone 10 mg IV is usually given for 3 to 5 days.
Symptomatic support therapy
Those with high cranial pressure may be dehydrated to lower cranial pressure. Physical cooling or antipyretic agents are used in cases of hyperthermia. Anti-epileptic drugs are given to terminate seizures in seizures. [3]
Prognosis
The rate of death and disability is high. The prognosis is closely related to the pathogenic organism, the condition of the body and the early and effective application of antibiotic therapy. A small number of patients may have sequelae such as mental retardation, epilepsy, and hydrocephalus.
Prevention
1) Early detection, early isolation and treatment.
2) Do good health education, improve environmental and personal hygiene.
3) Close contacts should take sulfa drugs, 1g per time/day for 3 days.
4) Preventive injection of Group A polysaccharide vaccine is available.