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MM 276-282; ID 1107-1124

ACUTE BACTERIAL MENINGITIS






NAME OF DISEASE:     Purulent meningitis
                                               Bacterial meningitis
                                               Epidemic cerebrospinal meningitis
                                               Cerebrospinal fever
                                               Spotted fever
                                               Sleeping Baby Jesus Syndrome
 

OVERVIEW:

The disease usually begins as an infection by normal body flora, of:

  1. The ear (otitis media) - Haemophilus influenzae
  2. The lung (lobar pneumoniae) - Streptococcus pneumoniae
  3. The upper respiratory tract (rhinopharyngitis) - Neisseria meningitidis, Haemophilus influenzae, Streptococcus, Group B
  4. The skin and subcutaneous tissue (furunculosis) S. aureus
  5. The bone (osteomyelitis) - S. aureus
  6. The intestine - E. coli
This localized infection develops into a bacteremia with a metastatic infection in the leptomeninges (arachnoid and pia mater), although meningitis can also result from cranial or spinal trauma. There is always some degree of concomitant encephalitis. The infection spreads throughout the subarachnoid space, involving the leptomeninges, brain and spinal cord. This may be exceedingly rapid in acute bacterial meningitis and death may occur in hours. Males are affected twice as often as females.

ETIOLOGICAL AGENT:

    Neonates (0-2 weeks)

        Escherichia coli
        Streptococcus, Group B
        Staphylococcus aureus
        Listeria monocytogenes
        Streptococcus, Group A

    Infants (½ - 3 months)

        Streptococcus, Group B
        Listeria monocytogenes
        Escherichia coli

    Children (3 months - 6 years)

        Haemophilus influenzae
        Neisseria meningitidis
        Streptococcus pneumoniae
        Staphylococcus aureus
        Mycobacterium tuberculosis

    "Normal" Adults (6-21 years)

        Neisseria meningitidis
        Streptococcus pneumoniae

    Diabetics, alcoholics, elderly, debilitated, diseased (untreated)

        Listeria monocytogenes
        Streptococcus pneumoniae
        Treponema pallidum

PATHOLOGY:

The extent of morbid change in the central nervous system is determined primarily by the duration of the meningitis before death. When the course has been fulminant, at most there may be only slight flattening of the gyri and a few polymorphonuclear leukocytes in sections of meninges and brain. If, as is usual, 6-10 days have passed before death, the leptomeninges are congested, an acute vasculitis, with fibrin deposition involves the smaller vessels, and there may be petechial lesions of the pia. An exudate rich in fibrin and neutrophilic granulocytes fills the sulci, and in some patients, it extends over the convolutions as well. Ventriculitis may be present and is common in neonatal meningitis. The exudate may involve the brain, although encephalitis, as it occurs in most adults and some children, is characterized by acute inflammation of the brain that is both diffuse (parenchymal) and focal (perivascular).

When meningococcemia is associated with fulminant disease (sudden onset of fever, malaise, abdominal pain, with purpura, cyanosis, hypotension, and death within 6-24 hours) both clinical and pathologic evidences of meningitis may be minimal or absent. The classic finding at necropsy is extensive hemorrhage into both adrenal glands--the anatomic component of the Waterhouse-Friderichsen syndrome.

The mechanism of pathology may be either:

    1. Endotoxemic shock

    2. Disseminated intravascular coagulation

Widespread vasculitis involving the arterioles and capillaries is actually the major lesion in patients with septicemic adrenal hemorrhage. Vasculitis afflicts the heart, causing diffusely distributed foci of myocarditis, and focal involvement of the conduction system. Acute vasculitis leads to plugging of the vessels with fibrin, resulting in focal myocardial necrosis with associated hemorrhage and neutrophilic infiltration. Such lesions have been present in more than three-fourths of patients who have died of meningococcal infections. Pulmonary edema and congestion consequent to acute myocarditis have been present in 78% of the fatal cases, and 30% of these have had pleural effusions.

Purpura is also a consequence of acute vasculitis - with meningococci in endothelial cells, necrosis of vessel walls, and fibrin plugged arterioles and capillaries. The mucous membranes of the oral cavity, the conjunctival and serosal surfaces, and occasionally, the glomeruli and adrenal glands, may be similarly afflicted. Hemorrhage and necrosis of the adrenal glands have been found in 48% of 200 fatal meningococcal infections. The lesions occur much more frequently with group C than with group B or group A N. meningitidis.

CLINICAL SYMPTOMS:

The manifestations of acute bacterial meningitis are independent of the etiological agent: They result from:

    1. Infection, manifestations of which are:

        a. Chills (due to venular constriction)

        b. Fever

        c. Malaise

        d. Headache (cephalgia)

        e. Myalgia

    2. Increased intracranial pressure, manifestations of which are:

        a. Headache

        b. Vomiting

        c. Eye effects

        d. Papilledema (late)

        e. Full fontanelle

        f. Enlarged cranium
 
 

TABLE I
SIGNS AND SYMPTOMS IN
INCREASED INTRACRANIAL PRESSURE

ADULTS INFANTS
EARLY Headache
Vomiting
Papilledema
Enlarged head
LATE Lethargy
Unilateral or bilateral 6th nerve
      palsy
Transtentorial or transforaminal
     syndromes
Lethargy or hyperirritability
Failure to thrive, vomiting

Bulging of anterior fontanel, distension of scalp veins, palpable separation of 
    cranial sutures, "setting sun" sign
Papilledema
Unilateral or bilateral 6th nerve 
   palsy
Transtentorial or transforaminal
   syndrome


 
 

TABLE II
TRANSTENTORIAL HERNIATION SYNDROME

EARLY SIGNS LATE SIGNS
PRE-TERMINAL SIGNS
Ipsilateral 3rd nerve palsy
Increasing stupor

Contralateral hemiparesis 
   (ipsilateral hemiparesis occurs
   as a false-localizing sign in 
   20% of cases)
Cortical blindness (rare)

Coma
Increasing blood pressure, bradycardia
Irregular respiration (Cheyne-Stokes, 
   central neurogenic hyperventilation)
Unilateral or bilateral decorticate posturing
Bilaterally dilated and fixed pupils
Loss of vestibulo-ocular reflexes
    (tested by calorie stimulation or 
    Doll's eye maneuver)
Loss of deep tendon reflexes
Loss of response to painful stimuli
Isoelectric EEG
Collapse of vasomotor and respiratory control

 

TABLE III
TRANSFORAMINAL HERNIATION SYNDROME

EARLY SIGNS LATE SIGNS PRE-TERMINAL SIGNS
Head tilt, nuchal ridgity, 
   suboccipital tenderness
Respiratory arrest (secondary to medullary compression)
Stupor or coma (secondary to anoxia rather than medullary
   compression)
Unilateral or bilateral decerebrate posturing (opisthotonos)
Circulatory collapse

*Note: Posterior fossa masses frequently produce upward (transtentorial) herniation as well as downward (transforaminal) herniation. Thus, the clinical signs of both syndromes may combine.
 
 

    3. Meningeal irritation (noted by elicitation of Brudzinski's and/or Kernig's sign)

        a. Stiff neck

        b. Spasms of the gracilis, sartorius and/ or bicepts femoris muscles

        c. Nuchal rigidity

        d. Opisthotonos

    4. Hemorrhage

        a. Petechia

        b. Purpura

        c. Ecchymosis

    5. Eye effects

        a. Photophobia

        b. Venous congestion of ocular fundi

        c. Unequal pupils

        d. Pupil dilation

        e. Sluggish reaction to light

        f. Squint

        g. Diplopia

        I. Papilledema

   6. Mentation

        a. Drowsiness

        b. Delirium

        c. Stupor

        d. Coma

The infant with meningitis may have signs of infection but more commonly is simply fretful and refuses food. Stroking of the head and frowning are equivalent to headache. Vomiting occurs early in the disease and is often repeated, leading to dehydration that may prevent the full fontanelle as associated with increased intracranial pressure. Fever may be absent and there may actually be hypothermia. As the disease progresses, apnea episodes, twitching, seizures (up to 30% of cases), opisthotonos, and coma may develop.

The mental state of the patient varies according to the stage and progress of the disease, and the age of the patient. Delirium is common in the early stages, but it may be followed by drowsiness, then stupor, and eventually, coma. Photophobia and a general hyperesthesia to all forms of stimuli are present. Venous congestion of the ocular fundi is common. Papilledema is quite uncommon at initial examination; indeed, if it is found when the patient is first seen, brain abscess or other intracranial disease must be suspected. The pupils may be unequal and react sluggishly; they may even become dilated and fixed as the disease progresses. Squint and diplopia with ptosis are common. Any of the ocular muscles may be paralyzed - most frequently, one or both external recti. Swallowing may be difficult owing to cranial nerve involvement. Although muscular power in the limbs is usually well-preserved, slight incoordination and tremor are common, and muscular hypotonia occurs quite regularly. Meningitis may be localized for a time to one hemisphere or the other, cause jacksonian convulsions, hemiparesis, or even hemianopia.

Infants with meningitis offer the greatest diagnostic problem because the manifestations are nonspecific. In older persons, early meningitis may be misdiagnosed as a flu-like illness, with fever, headache, and a minimal stiffness of the neck. The stiff neck may be ascribed to myalgia. Almost any other infection can cause fever and headache. If there is a history, supported by physical or other findings, consistent with otitis media, mastoiditis, sinusitis, or cavernous sinus thrombosis, secondary meningitis must be suspected. Similarly, patients with pneumoniae, osteomyelitis, bacteremia from any cause, or head trauma with or without rhinorrhea or otorrhea must be carefully studied for evidence of meningitis.

Skin rashes occur with meningococcemia, with or without meningitis. From the first to the third day, at least one-third of patients with meningococcal meningitis develop petechiae, most prominently in areas subjected to pressure; for example, axillary folds and the belt line. Purplish ecchymoses and maculopapular nodules up to 2 cm in diameter may also be present, tending to appear first on the trunk and later on the extensor surfaces of the thighs and forearms.

Examination of the cerebrospinal fluid (CSF) is the key to the definitive diagnosis of acute bacterial meningitis. The CSF should be examined in every patient in whom the clinical findings are consistent with even the possibility of meningitis, however minimal the manifestations. Examine the CSF for:

    1. Pressure

    2. Clarity

    3. Presence of microorganisms

    4. Presence of leukocytes

    5. Presence of RBCs

    6. Concentration of glucose

    7. Concentration of protein

    8. Concentration of gamma globulin

    9. Concentration of lactic acid

    10. Concentration of chloride

    11. Presence of endotoxin

    12. Bacterial antigens

DIFFERENTIAL DIAGNOSIS:

Bacterial Meningitis - pmn's outnumber monocytes, papilledema occurs late in disease when it occurs, acute onset. High lactate, low glucose of CSF.

Tubercular Meningitis - insidious onset, slight changes in CSF chemistry, positive tuberculin, low chloride.

Fungal Meningitis - insidious onset, history of lung infection, yeast cells in CSF, slight changes in CSF chemistry.

Syphilitic Meningitis - insidious onset, slight change in CSF chemistry, positive RPR test.

Parasitic Meningitis - acute onset, slight change in CSF chemistry, presence of IgM in CSF (Trypanosoma cruzi infection = Chagas' disease, sleeping sickness).

Viral Meningitis - acute onset, slight change in CSF chemistry. Monocytes outnumber PMN's.

Subarachnoid hemorrhage - red blood cells in CSF.

Meningioma - X-ray for tumor presence.

Meningismus - history of non-CNS viral disease ( a non-infective state resembling meningitis).

Brain Abscess - pmn's may outnumber monocytes, papilledema occurs early in disease, acute or insidious onset. Sterile CSF.

Tetanus - trismus, clean mentation.
 

THERAPY:

General: The risk of death during the early phases of acute bacterial meningitis usually relates to problems other than the infection itself. A combination of fever, dehydration secondary to vomiting, and decreased food and fluid intake with subsequent alkalosis often predisposes patients, especially young children, to seizures. Respiratory arrest or airway obstruction often follows; if significant CNS or myocardial hypoxia occurs, fatal cardiac arrhythmias or brainstem damage may result.

Procedures commonly employed include:

    1. Correction of fluid and electrolyte deficits.

    2. Provision for adequate oxygenation.

    3. Monitoring of cardiovascular function (Give a cardiac-active glycoside if necessary).

        a. Pulse

        b. Arterial blood pressure

        c. Central venous pressure

    4. Monitoring intracranial pressure - administer urea or mannitol to reduce cerebral edema.

    5. Administration of antibiotics -

        Empuric regimen

            Neonate (up to 1 month old) -     Ampicillin + Cefotoxime or Ampicillin + Gentamycin

            Neonate (1-3 months old)-         Ampicillin + Dexamethazone or Ampicillin + Dexamethazone + Cefotoxime

            Other (3 months - 50 years old)-     Cefotoxime + Vancomycin

            (Over 50 years old or alcoholic)-     Ampicillin + Cefotoxime
 

PREVENTION:

Purified polysaccharide vaccines are available for the prevention of infection by:

Neisseria meningitidis - each dose of the multivalent vaccine provides A, C, Y and W-135 capsular polysaccharides. Effective in children over 3 months of age.

Streptococcus pneumoniae (PNU-IMMUNE or Pneumovax)- each dose of the multivalent vaccine provides 23 types of capsular polysaccharide covering the majority of strains causing meningitis. Recommended for children over 2 years of age.

Streptococcus pneumoniae (Prevnar)- each dose of the multivalent vaccine provides 7 types of capsular polysaccharide conjugated to a non-toxic diphtheria toxin. Recommended for children at 2, 4, 6 and 12 months of age.

Haemophilus influenzae - each dose of the monovalent vaccine provides the capsular polysaccharide from serotype b organisms conjugated to a protein. Recommended for children at 2, 4, 6 and 15 months of age.
 

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