Meningitis

Meningitis is an inflammation of the membranes of the brain or spinal cord. Often the disease is infectious in nature and is one of the most common infectious diseases of the central nervous system.

Along with the envelopes, the brain substance (meningoencephalitis) can also be involved in the process. A complete clinical picture of meningitis can develop at a lightning speed - for several hours or days (acute meningitis) or for a longer time (subacute or chronic meningitis).

Acute aseptic meningitis syndrome is a moderately severe, viral infection prone to self-healing, causing inflammation of the brain membranes. Encephalitis is an inflammation of the brain tissue, usually accompanied by impaired consciousness, cognitive impairment or focal neurological symptoms.

[1], [2],

Epidemiology of meningitis

Viruses are the most frequent pathogens of acute aseptic meningitis. In large countries (USA) annually register 8-12 thousand cases. The introduction of modern diagnostic systems based on methods of molecular typing, allowed to identify the pathogen in 50-86% of cases of diseases.

Enteroviruses consider the cause of 80-85% of cases of all meningitis of viral etiology. The most often sick newborns and children due to the lack of specific antibodies. In Europe (Finland), the incidence of children of the first year of life reaches 219 per 100 thousand people. Of the population per year, while for children over the year - 19 per 100 thousand.

Arboviruses are the cause of meningitis transmitted by insects, they account for about 15% of all cases of the disease. It is this group of pathogens that is responsible for the occurrence of cases of tick-borne encephalitis.

Herpesviruses consider the cause of 0.5-3.0% of all aseptic meningitis, which often occurs as a complication in primary genital herpes (HSV 1 - herpes simplex virus type 2) and extremely rarely - with relapsing. In patients with immune disorders, meningitis can be caused by cytomegalovirus, Epstein-Barr virus, HSV type 1 and type 6. The most severe course of viral meningoencephalitis in patients without immunological disorders is associated with infections of HSV type 2, in patients with immune disorders, any viral neuroinfection acquires a life-threatening character.

Bacteria are an urgent problem due to the high lethality of meningitis caused by bacteria. The incidence in the world varies widely from 3 to 46 per 100 thousand people, the mortality varies considerably depending on the causative agent from 3-6% (Haemophilus influenzae) to 19-26% (Streptococcus pneumoniae) and 22-29% (Listeria monocytogenes). Aerobic Gram-negative bacteria (Klebsiella spp, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa) and staphylococci (S. Aureus, S. Epidermidis) are becoming increasingly important agents of meningitis in patients with CCI, neurosurgical operations, in patients with immunosuppression. The lethality with meningitis caused by staphylococci is between 14 and 77%.

Mushrooms. The most common are meningitis caused by candidias. About 15% of febrile patients with disseminated candidiasis have a CNS infection. Risk factors for cancer, neutropenia, chronic granulomatous diseases, diabetes, obesity. Meningitis caused by cryptococci (Cryptococcu neoformans) also develops against the background of immunological disorders. Approximately 6-13% of patients with AIDS develop meningitis caused by this microflora.

[3], [4], [5], [6], [7], [8], [9], [10],

What causes meningitis?

The causative agents of meningitis can be viruses, bacteria, spirochaetes, fungi, some protozoa and helminths.

Viruses

Enteroviruses, arboviruses, mumps virus, lymphocytic choriomeningitis virus, herpes viruses.

Bacteria

Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes, Streptococcus agalactiae, aerobic gram-negative bacteria - Klebsiella spp, E. Coli, Serratia marcescens, Pseudomonas aeruginosa, Salmonella spp., Staphylococcus aureus, S. Epidermidis, other bacteria - Nocardia meningitis, Enterococcus spp., anaerobes, diphtheria, Mycobacterium tuberculosis.

Spirochetes

Treponema pallidum, Borrelia burgdorferi.

Mushrooms

Cryptococcus neoformans, Candida spp, Coccidioides immitis.

Pathogenesis of meningitis

Penetration of pathogens into the subarachnoid space can occur in various ways, each of which has its own pathogenetic features. In most cases, it is not possible to establish precisely the mechanism of bacterial penetration into the central nervous system. With regard to bacterial meningitis, they are conventionally divided into primary (bacteria enter the subarachnoid space from mucous membranes) and secondary (spreading contact from closely located loci of infection, eg, ENT organs, or hematogenously, for example from the lungs or other distant foci of infection). After the penetration of pathogens into the submucosa, they enter the subarachnoid space with a current of lymph or blood, which is an ideal medium for their development due to stable temperature, humidity, nutrient availability, lack of humoral and cellular anti-infectious protection systems due to the presence of BBB. Reproduction of bacteria in the subarachnoid space does not limit anything until the moment of their phagocytosis by microglial cells playing in the central nervous system the role of tissue macrophages and triggering an inflammatory reaction. As a result of inflammation, the permeability of the capillaries of the central nervous system sharply increases, the exudation of proteins and cells occurs, the presence of which in CSF, in combination with clinical signs, confirms the presence of meningitis.

The main mechanisms of invasion of pathogens in the central nervous system

• Colonization by a pathogenic or conditionally pathogenic flora of the mucous membranes of the upper respiratory tract. The choice of the moment of invasion is associated with unfavorable conditions for the microorganism (supercooling, overstrain, disadaptation), when pathogens use an unknown mechanism to enter the submucosal layer. With the flow of lymph and blood, pathogens fall into the subarachnoid space.
• Defects of the integrity of tissues and liquorrhea as a result of congenital (fistula of the dura mater) or acquired (fracture of the base of the skull) disorders (mainly Streptococcus pneumoniae). As a rule, the disease is preceded by an increase in nasal or ear liquorrhea.
• Hematogenous dissemination Usually occurs after the formation of a primary focus of infection in various organs and tissues. Most often occurs against the background of pneumonia caused by pneumococci, which have a genetic affinity for the structures of the membranes of the brain. With massive hematogenous dissemination, in addition, there may be ischemic foci as a result of embolism with the formation of microabscesses in terminal sections of arterioles and capillaries that carry the danger of engaging brain tissue in the inflammatory process and the formation of encephalitic foci.
• Contact dissemination. Usually occurs as a result of the spread of infections of the ENT organs, after carrying out neurosurgical operations, as a result of infection of tissues with open TBI.
• Neuronal spread. It is characteristic for some viruses HSV (herpes simplex virus) of the 1 st and 6 th types, VZV (shingles virus).

Mechanism of CNS damage in viral infections

The penetration of viruses into the central nervous system occurs hematogenically (viremia) and neuronally. The virus must cross the epithelium to get into the blood, and the virus also gets into the bites of blood-sucking insects. From the blood, he enters the regional lymph nodes and other organs, including the central nervous system. In most cases, the virus actively replicates in the liver and spleen, creating conditions for massive secondary viremia, which usually leads to infection of the central nervous system. CNS lesion is accompanied by dysfunction of cortical and stem structures as a result of a combination of direct cytopathic action of viruses and immune reaction of the body. However, viral invasion is considered the most important starting point of the disease. In the brain parenchyma, neuronophagy, the presence of viral antigens and nucleic acids can be detected. After the encephalitis, some symptoms may remain forever, although there is no viral invasion. At a microscopic examination, demyelination and perivascular aggregation of immune cells are detected, with viruses and viral antigens absent. Meningitis and encephalitis are different infectious diseases, but sometimes they are very difficult to separate. All neurotropic viruses, with the exception of the rabies virus, are capable of causing meningitis, encephalitis and their combination - meningoencephalitis. The change in the clinical picture of the disease reflects the involvement of various parts of the brain in the infectious process. That is why in many cases it is initially very difficult to determine the shape, course, volume of the CNS lesion and to assume the outcome of the disease.

Mechanism of CNS damage in bacterial infections

When bacteria enter the subarachnoid space, their rapid multiplication occurs, which causes inflammation. Lymphogenous spread usually leads to inflammation, which is predominantly engaging in the subarachnoid space and the ventricular system. With hematogenous spreading, bacteria also enter the brain cavity, but, in addition, are able to form small diffusely located foci of inflammation in the brain, sometimes in the form of large foci, which soon appear as encephalitic. Practically in all cases of bacterial meningitis, intracranial hypertension associated with the hyperproduction of CSF and the violation of its rheological properties (increase in viscosity), edema of brain substance interstitial and vascular congestion, are noted for varying degrees of severity. High degree of intracranial hypertension and densification of the brain material create conditions for hernia and dislocation of the brain in the form of anteroposterior, lateral and helical displacements, which substantially disturb its blood circulation. Thus, microorganisms become a trigger for the development of inflammation, which complicates intracranial hypertension and vascular disorders that determine the outcome of the disease.

Symptoms of meningitis

In most cases, infectious meningitis begins with fuzzy precursors in the form of manifestations of a viral infection. The classic triad of meningitis - fever, headache and stiff neck - develops within hours or days. Passive bending of the neck is limited and painful, and rotation and extension are not. In cases of severe illness, rapid neck flexion of the patient lying on the back leads to involuntary bending of the legs in the hip and knee joints (Brudzinsky's symptom), and an attempt to extend the knee joint with the legs bent in the hip joints may encounter strong resistance (Kernig symptom). Rigidity of the neck muscles, symptoms of Brudzinsky and Kernig are called meningeal symptoms; they arise because the tension causes irritation of the motor nerve roots passing through the inflamed meningeal membrane.

Although in the early stages of the disease the substance of the brain is not involved in the inflammatory process, the patient may develop retardation, confusion, convulsions and focal neurological deficit, especially in the absence of treatment.

Viral meningitis: symptoms

Age and immune status of the patient in combination with the characteristics of the virus determine the clinical manifestations of infection. With enteroviral meningitis, the disease begins acutely, fever (38-40 ° C) for 3-5 days, weakness and headache. Half of patients notice nausea and vomiting. The leading signs of the disease are stiff neck muscles and photophobia. Children may experience seizures and electrolyte disturbances. When meningitis caused by HSV type 2, except for the symptoms of meningitis (neck tension, headache, photophobia), note the retention of urine, sensory and motor impairment, muscle weakness, repeated tonic-clonic convulsions. With infection caused by the Epstein-Barr virus, in addition, pharyngitis, lymphadenopathy, splenomegaly may occur.

Bacterial meningitis: symptoms

Characteristic features - acute onset, fever, headache, meningeal syndrome, signs of impaired brain function (decreased level of consciousness). It should be noted that meningeal syndrome (stiff neck muscles, positive symptoms of Kernig and Brudzinsky) may not occur in all patients with meningitis. Paresis of cranial nerves (III, IV, VI and VII) is observed in 10-20% of patients, seizures - more than 30%. Edema of the optic disc in the onset of the disease is noted in only 1% of patients, this indicates chronic intracranial hypertension and is not important for the diagnosis of meningitis. A high degree of intracranial hypertension is indicated by coma, hypertension, bradycardia and paresis of the third pair of cranial nerves.

[11], [12], [13], [14], [15]

Fungal meningitis: symptoms

The most acute clinical symptomatology develops with meningitis, caused by candidiasis, with meningitis of another etiology (cryptococci, coccidia) - gradually. As a rule, patients develop fever, headache, meningeal syndrome, the possibility of contact with the patient worsens, sometimes paresis of cranial nerves and focal neurological symptoms are noted. When cryptococcal meningitis is observed, the invasion of the optic nerve with a characteristic picture on the fundus. For meningitis caused by coccidia, a subacute or chronic course is typical, meningeal syndrome is usually absent.

Classification of meningitis

There are the following types:

• Viral infections of the central nervous system
• Acute aseptic meningitis syndrome
• Encephalitis
  • acute (allowed for a short period of time - several days),
  • chronic (the disease lasts several weeks or months)
• Meningoencephalitis
• Bacterial and fungal infections of the central nervous system

The most common forms of meningitis are bacterial and aseptic. Acute bacterial meningitis is a serious disease characterized by the presence of pus in the cerebrospinal fluid. Bacterial meningitis very quickly progresses and without treatment ends in a lethal outcome. Aseptic meningitis is characterized by a milder flow, the disease is usually resolved on its own; usually causative agents of aseptic meningitis are viruses, but there may be bacteria, fungi, parasites, as well as a number of non-infectious factors.

[16], [17], [18], [19]

Diagnosis of meningitis

Acute meningitis is a serious disease requiring emergency diagnosis and treatment. The first urgent diagnostic measures are blood sowing for sterility, as well as lumbar puncture followed by bacteriological study of cerebrospinal fluid (Gram staining and culture), biochemical analysis including determination of protein and glucose level, and cytological examination with differentiated cell counting. If the patient has symptoms of intracranial volumetric process (focal neurological deficit, congestive discs of optic nerves, impaired consciousness, epileptic seizures), before performing a lumbar puncture, CT should be done to exclude the possibility of wedging in the presence of an abscess or other voluminous formation.

The results of the analysis of cerebrospinal fluid can help in the diagnosis of meningitis. The presence of bacteria in a stained smear or the growth of bacteria in the seed is the basis for the formulation of the diagnosis of bacterial meningitis. In the Gram stain smear of the cerebrospinal fluid, about 80% of the cases are detected by bacteria, which are often identified already at this stage of the study. Lymphocytosis and the absence of pathogens in CSF testify to the use of aseptic meningitis, although they can also occur in the treatment of bacterial meningitis.

[20], [21], [22], [23], [24]

Analysis of cerebrospinal fluid with meningitis

For the diagnosis of meningitis of any etiology, a lumbar puncture with CMC smear microscopy, study of protein and sugar concentration, seeding and other diagnostic methods is mandatory.

Viral meningitis

CSF pressure usually does not exceed 400 mm of water column. Viral meningitis is characterized by lymphocytic pleocytosis within 10-500 cells, in some cases the number of cells can reach several thousand. Neutrophils at the onset of the disease (6-48 h) may be more than 50% of the cells, in this case, some experts recommend repeating the lumbar puncture after 5-8 h to see if the nature of the cytosis changes. The protein concentration is moderately elevated (less than 100 mmol / l). The glucose level is usually about 40% of the blood level.

Bacterial meningitis

CSF pressure usually exceeds 400-600 mm of water column. Characteristic is the predominance of neutrophils with a cytosis of 1000-5000 cells in 1 μl, sometimes more than 10,000. In approximately 10% of patients at the onset of the disease, the cytosis can be predominantly lymphocytic, more often in neonates with meningitis caused by L monocytogenes (up to 30% of cases) with low cytosis and a large number of bacteria in the CSF. Approximately 4% of patients with bacterial meningitis have cytosis in the CSF, usually they are newborns (up to 15% of cases) or children up to 4 weeks (17% of cases). Therefore, all CSF specimens should necessarily be stained with Gram, even in the absence of cytosis. Approximately 60% of patients show a decrease in the concentration of glucose in the CSF (<2.2 mmol / l) and a ratio of blood glucose and in the CSF below 31 (70% of patients). The concentration of protein in CSF increases in virtually all patients (> 0.33 mmol / L), this is considered a differential diagnostic feature with non-bacterial meningitis in patients who have not previously received antibiotics.

The staining of CSF smears by Gram is considered to be a quick and accurate method of detecting pathogens in 60-90% of cases of bacterial meningitis, the specificity of the method reaches 100%, correlates with the concentration of specific bacterial antigens and bacteria. At a bacterial concentration of 103 cfu / ml, the probability of detecting bacteria using Gram staining is 25%, at a concentration of 105 and higher, 97%. The concentration of bacteria may decrease in patients who have already received antibiotics (up to 40-60% if detected by staining and below 50% by sowing). It was shown that in neonates and children with bacterial meningitis and the isolation of bacteria from a CSF sample obtained during a diagnostic spinal puncture, the restoration of CSF sterility in 90-100% occurred within 24-36 hours after the onset of adequate antibacterial therapy.

[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35],

Fungal meningitis

With meningitis caused by candidiasis, pleocytosis averages 600 cells per 1 μl, the nature of pleocytosis can be both lymphocytic and neutrophilic. In microscopy, fungal cells are found in about 50% of cases. In most cases, it is possible to obtain fungal growth from CSF. In meningitis caused by cryptococci, CSF usually has low pleocytosis (20-500 cells), in 50% there is neutrophilic pleocytosis, the protein concentration is increased to 1000 mg% or more, which may indicate a block of subarachnoid space. For the detection of fungi a special staining is used, which allows obtaining positive results in 50-75%. With meningitis caused by coccidia, note eosinophilic pleocytosis, the causative agent is isolated in 25-50% of cases.

[36], [37], [38], [39], [40], [41], [42], [43]

Etiological diagnosis of meningitis

Viral meningitis

With the development of methods of molecular diagnostics (PCR), the effectiveness of diagnostics of viral infections of the central nervous system has significantly increased. This method reveals conserved (characteristic for this virus) areas of DNA or RNA, has a high sensitivity and specificity in the study of normally sterile media. This method almost supplanted virological and serological diagnostic methods due to high efficiency and rapidity (the study continues <24 h).

Bacterial meningitis

There are several methods for confirming the etiology of meningitis:

• Counter immunophoresis (the duration of the study is about 24 hours) allows the detection of antigens of N. Meningitidis, H. Influenzae, S. Pneumoniae, group B streptococci, E. Coli. The sensitivity of the method is 50-95%, the specificity is more than 75% - it allows to identify the antigens of N. Meningitidis, H. Influenzae, S. Pneumoniae, group B streptococci, E. Coli.
• Latex agglutination (duration of the test less than 15 min) allows to detect antigens of N. Meningitidis, H. Influenzae, S. Pneumoniae, group B streptococcus, E. Coli.
• PCR diagnosis (duration of the study less than 24 hours) allows to detect the DNA of N. Meningitidis and L. Monocytogenes, the sensitivity of the method is 97%, the specificity is about 100%.

[44], [45], [46]

Radiation diagnosis of meningitis

Skull examination using a computer and MRI is not used to diagnose meningitis. However, these methods are widely used to diagnose the complications of this disease. An unusually long period of fever, clinical signs of high ICP, the appearance of persistent local neurological symptoms or seizures, an increase in head size (newborns), the presence of neurological disorders, and the unusual duration of the CSF sanation process are considered indications for use. These studies are very effective for diagnosing liquorrhea in patients with meningitis due to fracture of the base of the skull, detection of fluid accumulation in the skull and accessory sinuses of the nose.

Treatment of meningitis

In the presence of symptoms of meningitis, antibiotic treatment of meningitis begins immediately after the sowing of blood. When doubting the diagnosis and the mild course of the disease, the appointment of antibiotics can be postponed until the results of the culture of the cerebrospinal fluid are obtained.

The CSF protein level <100 mg / dl for the first lumbar puncture is detected in approximately 14% of patients.

ATTENTION: pressure, cytosis and protein levels are approximate values; there are often exceptions. PML may also predominate in diseases characterized by lymphocytosis, especially in the early stages of viral infections or tuberculous meningitis. Changes in glucose content are less variable.