INFECTIONS OF THE NERVOUS SYSTEM

Prof. M. Gavriliuc, Department of Neurology, Medical and Pharmaceutical Nicolae Testemitsanu State University, Republic of Moldova

Cerebrospinal Fluid Circulation 1. The greater part of the cerebrospinal fluid is elaborated by the choroid plexus.

2. The CSF passes into the lateral ventricles. 3. The CSF flows through the interventricular foramen (Monro) into the third ventricle and way of the aqueduct of Sylvius into the fourth ventricle.

Cerebrospinal Fluid Circulation

4. Exits of CSF into the subarachnoid space: (1) through the foramen of Magendie in the roof of the fourth ventricle, thereby entering the cisterna magna or the cisterna cerebello-medullaris, (2) through either foramina of Luschka (situated at the extreme lateral portions of the fourth ventricle), thereby emptying into the cisterna pontis, (3) from the cisterna magna the cerebrospinal fluid may be directed over the cerebellar hemispheres to the cisterna superior.

Cerebrospinal Fluid Circulation

5. From the cisterna pontis the flow of the cerebrospinal fluid is forward to the cisterna interpeduncularis and cisterna chiamatis. From these cisternae the fluid sweeps upward over the surface of both lateral hemispheres, anteriorly, upward between the two hemispheres along the longitudinal fissure, over the corpus callosum, along the Sylvian fissure and over the temporal lobes. The fluid finally reaches the arachnoidal villi where, by a process of osmosis, it is emptied into the great venous dural sinuses, particularly the superior sagittal sinus.

We are protected from pathogenic microorganisms by immunological barriers.

Risk factor of infection

1.skin injury surgical operationdermatitistraumburn or scald 2.mocosal impairment drugchemicalsanticancerH2inhibitors... stomatitisviral infectionbacterial translocationsepsis 3.malnutrition hypoproteinvitamin deficiencyalcholic damage 4.artificials artificial substancecathetersendotracheal tube, urethral tube 5.retardation of blood flow decubitusskin ulceration 6.dysfunction of reticuloendotherial system liver cirrhosispost splenectomy 7.decreasing of immunity anti cancercancer patientsHIVDMsteroid hormone

INFECTIONS OF THE NERVOUS SYSTEM

The immediate effect of bacteria or other microorganisms in the subarachnoid space is to cause an inflammatory reaction in the pia and arachnoid, in the cerebrospinal fluid (CSF), and in the ventricles, involving all the structures that lie within or adjacent to these spaces.

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

ANATOMICAL CONSIDERATIONS

CATEGORIES Mononeuritis Multineuritis Polineuritis Plexitis Funiculitis Ganglionitis Radiculitis Poliradiculoneuritis

Peripheral nervous system

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

ANATOMICAL SUBSTRATUM

CATEGORIES Neuritis Ganglionitis Truncitis

Autonomic nervous system

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

ANATOMICAL CONSIDERATIONS

CATEGORIES CATEGORIES Leptomeningitis Arahnoiditis Pahimeningitis Leptopahimeningitis

Spinal and cerebral meninx

Meningitis

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

ANATOMICAL CONSIDERATIONS Cerebral parenchyma

CATEGORIES Polioencephalitis Encephalitis Leucoencephalitis Panencefalit Transversal Myelities Poliomielit

Medullar parenchyma

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

ANATOMICAL CONSIDERATIONS Cerebral and medullar parenchyma Meninx and cerebral and/or medullar parenchima

CATEGORIES Encephalomyelitis Meningoencephalitis Meningomyelitis Meningoencephalomyelitis

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

ANATOMICAL CONSIDERATIONS

CATEGORIES ANATOMICAL CONSIDERATIONS Arteriitis Phlebitis Pahimeningitis Sinusitis (cerebral)

Cerebral and/or medullar vessels

Vasculitis

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

Evolutional criterion: acute subacute chronic

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

INFECTION

NAME
ADN (parvoviridae, papovaviridae, adenoviridae, herpetoviridae, poxviridae, hepanaviridae) ARN (retroviridae, picornaviridae, togaviridae, bunzaviridae, coronaviridae, ortomyxoviridae, paramyxoviridae, rabdoviridae, arenaviridae, retroviridae) Other Chlamydia psittaci

VIRUSES

CHLAMYDIES
Chlamydia trachomatis

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

INFECTION MYCOPLASMS RICKETSIES BACTERIES

NAME
Mycoplasmataceae Family Acholeplasmae Family Ricketsia Coxiella Rochalimea Group B Streptococci, Gram-negative enteric bacilli (Escherichi Colli), Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae

INFECTIONS OF THE NERVOUS SYSTEM

CLASSIFICATION

INFECTION FUNGAL

NAME
Candida, Histoplsma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Actinomyces israelii, Nocardia, Aspergillus etc. Entamoeba histolytica, Balantidium coli, Giardia lamblia, Plasmodium, Babesia, Leishmania, Toxoplasma, Pneumocystis carinii). Trichinella spiralis, Schistosoma, Ancylostoma

PROTOZORAE

PARASITIC

duodenalis i Necator americanus, Strongyloide etc.

INFECTIONS OF THE NERVOUS SYSTEM

ETIOLOGIC AGENTS OF VIRAL MENINGITIS Herpes simplex virus types 1 and 2

Enteroviruses
Mumps HIV Lymphocytic choriomeningitis virus Epstein-Barr virus Influenza virus types A and B

PATHWAYS OF INFECTION

Respiratory passages ( Mumps, measles, and varicella) Oral-intestinal route (Polioviruses and other enteroviruses) Inoculation, as a result of the bites of animals (e.g., rabies) mosquitoes (arthropod-borne or arbovirus infections). Oral or genital mucosal route (HSV). Transplacentally (rubella virus, CMV, and human immunodeficiency virus (HIV).

ACUTE MENINGITIS (LEPTOMENINGITIS)

Clinical Features

MENINGITICAL TRIAD:
1. General inflammatory signs 2. Positive signs of meningeal irritation 3. CSF meninigitical syndrome.

ACUTE MENINGITIS (LEPTOMENINGITIS)

Diagnostic Workup

Once meningitis is suspected, lumbar puncture provides the necessary confirming diagnostic information. Typically, CSF opening pressures are elevated (greater than

180 mm H2O). CSF protein concentrations are increased due to the disruption of the blood-brain barrier by inflammation in over 95% of cases, and hypoglycorrhachia (greater than 50 mg/dl) may be seen in up to 60% of patients, although less commonly in patients with shunt infections. Radiographic procedures have a limited role in the diagnosis of acute bacterial meningitis. Cranial CT or MRI scanning is suggested in the patient with a focal neurologic exam or papilledema even if bacterial meningitis is suspected, in order to evaluate the risk of herniation following lumbar puncture due to a potential intracranial mass lesion.

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

Epidemiology and Risk Factors

Enteroviral infections occur primarily in the summer and autumn months in temperate climates; infants, young children, and immunocompromised patients are at greatest risk of infection. The enteroviruses comprise a total of 68 distinct serotypes of human pathogens, but the most common enteroviruses that cause aseptic meningitis are the coxsackieviruses B5, B3, B4, and A9; the echoviruses 30, 11, 7, 9, 6, 4, and 18; and enteroviruses 70 and 71.

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

Pathogenesis and Pathophysiology

Enteroviruses may enter the host through the mucosal surfaces of the gastrointestinal or respiratory tract. Enteroviruses are acquired most commonly by fecal-oral contamination and, less commonly, via aerosolized respiratory droplets. Most enteroviruses spread to the CNS via the bloodstream, but a small percentage may reach the CNS by direct neural spread from nerves terminating in the intestinal tissue. Virus traverses the blood-brain barrier either at the choroid plexus, where it may infect endothelial cells and spread into the cerebrospinal fluid causing a meningitis, or at the endothelium of the cerebral capillary cells in the brain parenchyma causing an encephalitis.

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

The clinical Presentation

The clinical presentation of aseptic meningitis includes fever (38 to 40 C), severe headache, nausea and vomiting, photophobia, and nuchal rigidity.

Neurological abnormalities are rare, and enteroviral meningitis in otherwise healthy children and adults is rarely associated with severe disease or poor outcome.

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

Differential Diagnosis

The diagnosis of enteroviral aseptic meningitis is based on examination of the cerebrospinal fluid (CSF).

The opening pressure should be normal or slightly increased, and there is a mild lymphocytic pleocytosis, a normal or slightly increased protein concentration, and a normal glucose concentration. The white blood cell count typically is less than 1000 cells/mm3 .

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

Differential Diagnosis

At the present time, isolation of an enterovirus by CSF viral culture is the gold standard for diagnosis of an enteroviral CNS infection.

When an enterovirus is isolated from a non-CSF site (throat, stool, serum, urine) in conjunction with a CSF pleocytosis and an absence of bacteria by Gram's stain or the latex agglutination technique, enteroviral meningitis is the presumptive diagnosis. An enterovirus isolated from a nonCSF site may, however, be unrelated to the CNS infection.

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

Management

Because the majority of enteroviral infections are spread by the fecal-oral route, enteroviral infections are best prevented by proper handwashing techniques. Infants and children are at particular risk for these infections, and good hygiene, including parental handwashing after urine and stool diaper changes and washing the hands of the infant or child before eating, can reduce the transmission of these infections.

ENTEROVIRAL (Echoviruses and Coxsackieviruses) ASEPTIC MENINGITIS

Management

There is no specific antiviral therapy for enteroviral CNS infection. Intravenous immune globulin has been used to treat enterovirus infections in newborns and in patients with agammaglobulinemia and other immunodeficiency states with good success, but it is not recommended in children and adults with uncomplicated enteroviral aseptic meningitis.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Epidemiology and Risk Factors

The natural reservoir for the lymphocytic choriomeningitis virus (LCMV) is the common house mouse.
Hamsters and laboratory animals can also be infected with this virus.

Most human infections result from contact with house mice.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Pathogenesis and Pathophysiology

The LCMV is a member of the arenavirus family and is maintained in nature primarily by vertical intrauterine infection in mice, hamsters, and rodents, producing a chronic asymptomatic infection in the offspring.
These animals shed the virus in saliva, nasal secretions, semen, milk, urine, and feces.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Pathogenesis and Pathophysiology

The route of transmission to humans remains unknown but is presumed to occur through contamination of open cuts or aerosolized spread of virus. There is no evidence of person- toperson transmission of LCMV infection.
Local replication of LCMV is followed by dissemination to the reticuloendothelial system with a subsequent viremia. The CNS is infected during the course of the viremia.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Clinical Manifestations

In patients with aseptic meningitis there is often a history of a biphasic illness.

The first stage resembles an influenza-like illness. This is then followed by a symptomfree period of time varying from a few days to 3 weeks, which is followed in turn by the acute onset of high fever, headache, vomiting, and signs of meningeal irritation.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Differential Diagnosis

The diagnosis of LCMV infection can be made by the appearance of IgM antibodies in a serum sample or by a fourfold or greater rise in antibody titer between the acute and convalescent serum samples.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Differential Diagnosis

The classic cerebrospinal fluid abnormalities include the following: (1) a lymphocytic pleocytosis of 300 to 3000 cells/mm3 , and (2) hypoglycorrhachia. LCMV is one of the few etiological agents of an aseptic meningitis with hypoglycorrhachia.
LCMV can be isolated from the CSF. The diagnosis of congenital LCMV infection is based on the clinical presentation and laboratory evidence of persistently high IgG immunofluorescent antibody (IFA) titers.

ARENAVIRUS (Lymphocytic Choriomeningitis Virus) ASEPTIC MENINGITIS

Management

Prevention of LCMV infection is the priority.

Laboratory animals acquired from areas where arenaviruses are indigenous should be tested for LCMV infection. Pregnant women should avoid contact with laboratory and household mice and hamsters. LCMV aseptic meningitis in children and adults is self-limited and complete recovery is the rule.

ACUTE BACTERIAL MENINGITIS

Epidemiology and Risk Factors

There are approximately 25,000 cases of bacterial meningitis in the United States each year, but this disease is much more prevalent in developing countries. Group B streptococci and gramnegative enteric bacilli are the etiological organisms of the majority of cases of bacterial meningitis during the neonatal period in developed countries.
In underdeveloped countries, gramnegative bacilli, predominantly Escherichia coli, are the most common pathogens.

ACUTE BACTERIAL MENINGITIS

Epidemiology and Risk Factors

Risk factors that predispose the newborn to bacterial meningitis include maternal infections, particularly of the urinary tract and uterus, obstetrical risk factors, including prolonged rupture of membranes and birth trauma, prematurity, low birth weight (less than 2500 g), congenital anomalies, perinatal hypoxia/ asphyxia, cardiopulmonary resuscitation and monitoring, prolonged ventilatory support, and intravenous lines.

ACUTE BACTERIAL MENINGITIS

Epidemiology and Risk Factors

After the neonatal period, Streptococcus pneumoniae and Neisseria meningitidis are the most common etiological agents of bacterial meningitis. Haemophilus influenzae type b (Hib) was the leading cause of bacterial meningitis in young children before the widespread use of the Hib conjugate vaccine. The latter has resulted in a marked reduction in the incidence of invasive infections caused by Hib in the United States.

Streptococcus pneumoniae

Staphylococcus aureus

Klebsiella pneumoniae

Pseudomonas aerginosa Mucoid type form biofilm

Pseudomonas aerginosa Unmucoid type Phagocyted by neutrophil

ACUTE BACTERIAL MENINGITIS

Epidemiology and Risk Factors

N. meningitidis causes meningitis primarily in children and young adults, with the majority of cases occurring in individuals under age 30. Major epidemics are heralded by disease occurring in older age groups.
The "meningitis belt" of sub-Saharan Africa refers to areas of Africa in which there are repeated epidemics of serogroup A meningococcal meningitis.

ACUTE BACTERIAL MENINGITIS

Epidemiology and Risk Factors

S. pneumoniae is the most common causative organism of community-acquired bacterial meningitis in the adult.
Pneumonia and acute and chronic otitis media are important antecedent events. Chronic disease, specifically alcoholism, sickle cell anemia, diabetes, renal failure, cirrhosis, splenectomy, hypogammaglobulinemia, and organ transplantation are predisposing conditions for pneumococcal bacteremia and meningitis.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

The most common bacteria that cause meningitis, N. meningitidis and S. pneumoniae, initially colonize the nasopharynx by attaching to the nasopharyngeal epithelial cells.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

The organisms are able to attach to the nasopharyngeal epithelial cells via an interaction between bacterial surface structures, such as the fimbriae of N. meningitidis and host cell surface receptors.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

The bacteria are then either carried across the cell in membrane-bound vacuoles to the intravascular space or invade the intravascular space by creating separations in the apical tight junctions of columnar epithelial cells.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

S. pneumoniae and N. meningitidis are both encapsulated bacteria, and once they gain access to the bloodstream, they are successful in avoiding phagocytosis by neutrophils and classic complementmediated bactericidal activity because of the presence of the polysaccharide capsule.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

Bacteria that are able to survive in the circulation enter the CSF from the bloodstream through the choroid plexus of the lateral ventricles and other areas of altered blood-brain barrier permeability.
The CSF is an area of impaired host defense because of a lack of sufficient numbers of complement components and immunoglobulins for the opsonization of bacteria.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

Bacteria multiply rapidly in the subarachnoid space. Both the multiplication of bacteria and the lysis of bacteria by bactericidal antibiotics result in the release of bacterial cell wall components.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

These induce the formation of the inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), by monocytes, macrophages, brain astrocytes, and microglial cells, which leads to altered blood-brain barrier permeability and the recruitment of polymorphonuclear leukocytes.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

This process results in the formation of a purulent exudate in the subarachnoid space, which is the basis for the neurological complications of bacterial meningitis.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

The alteration in blood-brain barrier permeability during bacterial meningitis results in vasogenic cerebral edema, which contributes to increased intracranial pressure. It also allows for the leakage of plasma proteins into the CSF that contribute to the inflammatory exudate in the subarachnoid space.

Contrast enhanced T1-weighted MR image of patient with meningitis. Diffuse pial meningeal enhancement.

ACUTE BACTERIAL MENINGITIS

Pathogenesis and Pathophysiology

The purulent exudate in the subarachnoid space interferes with the resorptive function of the arachnoid granulations. As resorption is obstructed, CSF dynamics are altered, and there is transependymal movement of fluid from the ventricular system into the brain parenchyma, which contributes to interstitial edema.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

The classic presentation of bacterial meningitis is headache, fever, stiff neck, and an altered level of consciousness, but the clinical symptoms and signs may vary depending on the age of the patient and the duration of illness before presentation.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

In children and adults, the symptoms and signs of bacterial meningitis are fever, headache, vomiting, photophobia, nuchal rigidity, lethargy, confusion, or coma.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

The typical rash of meningococcemia is a petechial-purpuric rash that develops on the trunk, lower extremities, mucous membranes, conjunctiva, and occasionally on the palms and soles.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

Cranial nerve palsies, and most notably sensorineural hearing loss, are a common complication of bacterial meningitis and may be present early in the course of the illness. A stiff neck is the pathognomonic sign of meningeal irritation, resulting from a purulent exudate or hemorrhage in the subarachnoid space.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

Nuchal rigidity or meningismus is present when the neck resists passive flexion. Kernig's sign is also a classic sign of meningeal irritation.
Jozef Brudzinski described at least five different meningeal signs. His best known sign, the nape of the neck sign, is elicited with the patient in the supine position and is positive when passive flexion of the neck results in spontaneous flexion of the hips and knees.

CT scan of thickening meninges CT demonstrates contrast enhancement of thickening meninges and multiple intraparenchymal enhancing lesions.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

Seizures occur in 40 percent of patients with bacterial meningitis typically during the first week of illness.

The etiology of seizure activity can be attributed to either one or a combination of the following: (1) fever; (2) cerebrovascular disease consisting of either focal arterial ischemia, infarction or cortical venous thrombosis with hemorrhage; (3) hyponatremia; (4) subdural effusion or empyema producing a mass effect; and (5) antimicrobial agents (e.g., imipenem, penicillin).

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

Raised ICP is an expected complication of bacterial meningitis and presents as one or a combination of the following clinical signs: (1) an altered level of consciousness; (2) the Cushing reflex--bradycardia, hypertension, and irregular respirations; (3) dilated, nonreactive pupil or pupils; (4) unilateral or bilateral cranial nerve six palsies; (5) papilledema; (6) neck stiffness; (7) hiccups; (8) projectile vomiting; and, (9) decerebrate posturing.

ACUTE BACTERIAL MENINGITIS

Clinical Features and Differential Diagnosis

The differential diagnosis includes viral meningoencephalitis, fungal meningitis, tuberculous meningitis, focal intracranial mass lesions, subarachnoid hemorrhage, Rocky Mountain spotted fever, and neuroleptic malignant syndrome.

ACUTE BACTERIAL MENINGITIS

Evaluation

The gold standard for the diagnosis of bacterial meningitis is the examination of the CSF. The classic CSF abnormalities in bacterial meningitis are (1)an increased opening pressure;

(2) a polymorphonuclear leukocytic pleocytosis;

(3) a decreased glucose concentration; and (4) an increased protein concentration.

Meningococcal Meningitis: Head CT demonstrates enlargement of the temporal horns.

Meningococcal meningitis: Grossly purulent exudate is seen in the leptomeninges.

ACUTE BACTERIAL MENINGITIS

Management

Empirical therapy of bacterial meningitis in adults should include a combination of ceftriaxone (2 g intravenously twice daily) or cefotaxime (8 to 12 g/d intravenously in divided doses q 4 hr) plus vancomycin (500 mg intravenously q 6 hr). In the older adult and in the immunocompromised adult in whom L. monocytogenes may be the etiological organism, ampicillin (12 g/d in divided doses q 4 hr) should be added to this regimen.

ACUTE BACTERIAL MENINGITIS

Management

It is also entirely reasonable to use dexamethasone for bacterial meningitis. The recommended dose is 0.6 mg/kg/d in four divided doses (0.15 mg/kg/dose) given intravenously for the first 4 days of antimicrobial therapy. The first dose of dexamethasone should be administered 20 minutes before the first dose of antimicrobial therapy.

Dexamethasone is beneficial in preventing the neurological complications of bacterial meningitis by decreasing meningeal inflammation.

ACUTE BACTERIAL MENINGITIS

Management

The present recommendations are to limit the initial rate of intravenous fluid administration to approximately three quarters of the normal maintenance requirements (or 1000 to 1200 ml/m2 / 24 hr). The intravenous fluid should be a multielectrolyte solution containing between one quarter and one half normal saline and potassium at 20 to 40 mEq/L in 5 percent dextrose. Once the serum sodium concentration increases above 135 mEq/L, the volume of the fluids administered can be gradually increased.

ACUTE BACTERIAL MENINGITIS

Management

The treatment of raised ICP in bacterial meningitis includes one or more of the following: (1) elevation of the head of the bed 30 degrees;
(2) hyperventilation to maintain the PaCO2 between 25 to 33 mm Hg;

(3) mannitol 1.0 g/kg bolus intravenous injection, then 0.25 to 0.5 g/kg intravenous every 3 to 5 hours to achieve a serum osmolarity of 295 to 320 mOsm/L;
(4) dexamethasone 0.15 mg/kg q 6 hr; and (5) pentobarbital coma with a loading dose 5 to 10 mg/kg administered intravenously at a rate of 1 mg/kg/min and a maintenance dose of 1 to 3 mg/kg/hr.

ACUTE BACTERIAL MENINGITIS

Management

The development of seizure activity should be anticipated in the patient with bacterial meningitis. Seizure activity occurs in approximately 30 to 40 percent of children with acute bacterial meningitis and in more than 30 percent of adults with pneumococcal meningitis, typically occurring in the first few days of the illness.

There is an increased risk of epilepsy following bacterial meningitis especially in those individuals who have seizures in the first few days of infection.

TUBERCULOUS MENINGITIS
Epidemiology and Risk Factors

Tuberculosis and CNS tuberculosis continued to be prevalent in developing countries. CNS tuberculosis is considerably more frequent in individuals with AIDS and tuberculosis involving other organ systems than in immunocompetent persons with tuberculosis. In some parts of the world, the most common AIDS-associated CNS infection is tuberculous meningitis.

Tuberculous meningitis. MRI of the brain.

Intracranial tuberculoma: Caseating granuloma (1) Contrast-enhanced axial CT shows numerous conglomerate areas of dense ring-enhancements at grey-white matter junction of left fronto-parietal lobe. Extensive low-attenuating white matter edema is seen at left cerebral hemisphere.

Intracranial tuberculoma: Caseating granuloma (3) T2-weighted axial image shows lobulated low T2 signal lesion with specks of central high signal corresponding to central caseation. Surrounding high T2-signal edema is appreciated.

Contrast enhanced T1-weighted Mr image of Tuberculous meningitis.

TUBERCULOUS MENINGITIS Pathogenesis

and Pathophysiology

Tuberculous meningitis develops from the hematogenous spread of tubercle bacilli to the meninges from a pulmonary source of acute infection. Isolated miliary tubercles form in the parenchyma of the brain or the meninges during the hematogenous dissemination of tubercle bacilli during the course of the primary infection or episodically from the endogenous reactivation of latent tuberculosis elsewhere in the body.

TUBERCULOUS MENINGITIS
Clinical Features

Acute meningoencephalitis characterized by coma, raised intracranial pressure, seizures, and focal neurological deficits or a slowly progressive illness with persistent and intractable headache followed by confusion, lethargy, and cranial nerve deficits. Fever may or may not be present in the course of this infection.

TUBERCULOUS MENINGITIS
Clinical Features

The sixth cranial nerve is the most frequently affected by tuberculous meningitis followed by the third, fourth, seventh, and less commonly, the second, eighth, tenth, eleventh, and twelfth cranial nerves. Hemiparesis may develop as a result of ischemic infarction in the medial striate and thalamoperforating arteries. Seizures are an infrequent presenting sign, although more than 50 percent develop seizures during the initial hospitalization.

TUBERCULOUS MENINGITIS
Clinical Features

In patients with an acute meningoencephalitis syndrome, coma may evolve rapidly and is because of increased ICP from both cerebral edema and communicating and obstructive hydrocephalus. The clinical syndrome of tuberculous encephalopathy is characterized by convulsions, stupor, coma, involuntary movements, paralysis, and decerebrate spasms or rigidity with or without clinical signs of meningitis or CSF abnormalities of tuberculous meningitis.

TUBERCULOUS MENINGITIS
Clinical Features

The combination of an unrelenting headache (+/- low grade fever) with malaise and anorexia and a CSF lymphocytic pleocytosis with a mild decrease in the glucose concentration is suggestive of tuberculous meningitis.

TUBERCULOUS MENINGITIS
Clinical Features

The combination of an unrelenting headache (+/- low grade fever) with malaise and anorexia and a CSF lymphocytic pleocytosis with a mild decrease in the glucose concentration is suggestive of tuberculous meningitis.

TUBERCULOUS MENINGITIS
Clinical Features

The classic CSF abnormalities in tuberculous meningitis are as follows:

(1) an elevated opening lumbar pressure; (2) increased WBC count between 10 to 500 cells/mm3 with a predominance of lymphocytes;

(3) an elevated protein concentration in the range of 100 to 500 mg/dL;

(4) a decreased glucose concentration (the median glucose concentration is approximately 40 mg percent); and, (5) a positive culture in 75 percent of patients requiring 3 to 6 weeks for growth.

TUBERCULOUS MENINGITIS
Clinical Features

The PCR technique and other molecular diagnostic techniques for the detection of M. tuberculosis DNA in the CSF hold the greatest promise. The sensitivity of the PCR technique for the detection of M. tuberculosis DNA in CSF is approximately 54 percent; however, false-positive results occur with rates of 3 to 20 percent.

EMPIRICAL THERAPY FOR TUBERCULOUS MENINGITIS

Drug Isoniazid (INH) Pyridoxine Rifampin Pyrazinamide Ethambutol* Streptomycin Dexamethasone Prednisone 10 mg/kg/d 30 mg/kg/d 15 to 25 mg/kg/d 20 to 40 mg/kg/d 0.15 mg/kg every 6 hr 1 mg/kg/d 0.15 mg/kg every 6 hr 1 mg/kg/d Dosage Children 10 mg/kg/d once daily Adults 300 mg/d 50 mg/d 600 mg/d 30 mg/kg/d 15 to 25 mg/kg/d

*When antimicrohial resistance is suspected. The American Academy of Pediatrics recommends a combination of INH, rifampin, pyrazinamide, and streptomycin for tuberculous meningitis in children. For altered consciousness, papilledema, focal neurological signs, impending herniation, spinal block, hydrocephalus. For intractable headache, papilledema with otherwise normal neurological examination

ACUTE MENINGITIS

"Knowledge is of two kinds. We know a subject ourselves, or we know where we can find information on it." -- Samuel Johnson