Case Based Pediatrics For Medical Students and Residents
Department of Pediatrics, University of Hawaii John A. Burns School of Medicine
Chapter VI.14. Meningitis
Raul Rudoy, MD, MPH
April 2003

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Case 1

A six month old male presents to the emergency department with a history of lethargy. He was seen 3 days ago with fever and URI symptoms, diagnosed with otitis media and treated with oral amoxicillin. This morning he had become irritable and was less active than usual. He has vomited three times and his urine output is noticeably decreased. He has no diarrhea.

Exam: VS T 40.0, P 90, R 30 (irregular), BP 120/90, weight 8kg. He is lethargic and arousable only to painful stimuli. His anterior fontanel is full and tense, and he has questionable neck rigidity. His TMs are red and bulging. His pupils are reactive, but his eyes do not focus well on his parents. His heart, lungs and abdomen are normal. His color and perfusion are good. He has no petechiae. He moves all his extremities weakly and his DTRs are hyperactive.

A CBC, blood culture and chemistry panel are drawn. An IV is started. Since an increased ICP (intracranial pressure) is suspected, a lumbar puncture (LP) is initially delayed and he is immediately given 500 mg of ceftriaxone IV. A stat CT scan of the brain is normal, so an LP is done and the CSF (cerebrospinal fluid) is visibly hazy. An infectious disease consultant is called to inquire about IV dexamethasone and vancomycin. Both are recommended and given. The CSF results return 1 hour later showing 450 WBCs, 95% segs, 5% monos, total protein 75, glucose 25 mg/dl. Gram stain of the CSF shows many WBCs with few gram positive cocci. He is admitted to the pediatric ICU.


The clinical presentation of this patient, with a very rapidly evolving febrile illness, changes in sensorium and evidence of increased intracranial pressure, is very compatible with a diagnosis of CNS (central nervous system) infection. Bacterial meningitis occurs more frequently between the ages of 2 months and two years. Acquisition of infected aerosolized particles, with initial colonization of the nasopharynx, is followed by subsequent replication in the regional lymph nodes, invasion, septicemia and CNS infection. The lack of anticapsular antibodies increases the risk of invasion. Rarely, the infection is due to spread from a contiguous focus such as the sinuses, the middle ear, or the mastoids. Bacterial meningitis secondary to otitis media is an uncommon phenomenon, but when it does occur, it is usually septicemic in origin, rather than due to direct extension.

Manifestations of bacterial meningitis are variable and depend upon the child's age and the duration of illness. In young infants, evidence of meningeal inflammation may be minimal and only irritability and poor feeding may be present. Body movements of infants with meningitis result in pain, accordingly a strong suspicion of CNS infection is aroused when the child does not wish to be handled but prefers to remain motionless. Such paradoxical irritability (which worsens when the child is carried, rocked or gently bounced), is highly suggestive of meningitis.

The older child will present with more clinical findings, such as nuchal rigidity, vomiting, lethargy and photophobia. Most cases of meningitis will be either of bacterial or viral etiology. Common bacterial causes in this age group include Streptococcus pneumonia (pneumococcus) and Neisseria meningitidis (meningococcus). The advent of a very efficacious vaccine against H. influenzae type B, has resulted in an almost complete disappearance of meningitis due to this etiological agent. Prior to this vaccine, this was the most common cause of bacterial meningitis.

An LP is indicated in patients with clinical findings compatible with meningitis. Strong consideration should be given to delaying the LP in patients with clinical findings of increased intracranial pressure. However, antibiotic administration should not be delayed by this. Antibiotics must still be given immediately once bacterial meningitis is suspected. The patient in our case has evidence of increased intracranial pressure since he has decreased sensorium, a bulging tense fontanel, hyperactive reflexes and changes in the vital signs such as a decreased pulse rate, hypertension and irregular respirations (Cushing's triad). Accordingly, caution should be taken before performing the LP due to the possibility of precipitating herniation. A CT scan of the head is a very rapid and accurate means to confirm increased intracranial pressure and if present, measures such as the administration of mannitol and hyperventilation, after rapid sequence intubation, should be instituted before the LP is done. Analysis of the CSF is usually very useful in confirming the diagnosis of bacterial meningitis. Acute bacterial meningitis is characterized by an elevated CSF white count with a predominance of polymorphonuclear cells (neutrophils), a decreased CSF glucose level, an increased protein value and a positive gram strain and culture. Administration of oral antibiotics prior to the LP, do not greatly modify the LP results, except for a slight decrease in the rate of identifying the organism on gram strain and cultures.

The treatment of meningitis is directed at reducing the damage produced by the inflammatory response by maintaining adequate cerebral perfusion with the use of adequate amounts of intravenous fluids and agents that reduce intracranial pressure and by treating the infection. The use of a third generation cephalosporin such as cefotaxime (50 mg/kg dose every 6 hours) or ceftriaxone (100 mg/kg day in one dose) provides coverage for most of the agents responsible (pneumococcus, meningococcus, H. influenzae type B) for meningitis except for penicillin-resistant pneumococcus which require the addition of vancomycin. Antibiotics used to treat meningitis must reliably penetrate the blood brain barrier in addition to reliably cover the organisms involved. The duration of treatment is dictated mostly by the clinical course but usually is 5 to 7 days for meningococcal infections and 10 days for infections due to pneumococcus. Neonatal meningitis has a different group of etiologic bacteria and antibiotics which are covered in the chapter on neonatal sepsis.

The survival of patients with bacterial meningitis has improved but it still remains a disease with high morbidity. Approximately half of those with S. pneumoniae and 15 percent of those with H. influenzae meningitis will develop neurological sequela. Cerebral infarction occurs in 5 to 20 percent of the patients as a result of localized inadequate perfusion due to local thrombosis, arteriolar vasculitis and phlebitis secondary to the inflammatory response. Sensorineural hearing loss is the most common sequela occurring in approximately 15 percent of cases. The hearing loss is usually severe, bilateral and permanent, and it occurs during the first few days of the infection. Penetration of bacteria through the internal auditory canal results in inflammation and destruction of the auditory nerve. Reduction in the incidence of hearing loss was reported with the use of corticosteroids (dexamethasone) for cases of H. influenzae meningitis, but proof supporting the benefit of corticosteroids with other causes of bacterial meningitis is not as evident. The use of corticosteroids is currently controversial due to the decrease in cases of H. influenzae meningitis (due to routine H. influenzae vaccine) and the fact that most cases of bacterial meningitis are now caused by pneumococcus and meningococcus, for which the benefit of corticosteroids is less proven.

Primary prevention of meningitis is accomplished by the administration of H. influenzae type B and S. pneumoniae vaccines to infants. Meningococcal vaccine is also available, but it is not routinely recommended, except adolescents and adults residing in dormitories or military barracks. Secondary prevention, with antibiotics such as rifampin is recommended for close contacts of patients with invasive H. influenzae type B and N. meningitis disease (but not for pneumococcal meningitis).


Case 2

A three year old female presents to the emergency department with a two day history of headache, nausea, vomiting and fever. She was seen by a physician two days ago who diagnosed otitis media and prescribed amoxicillin. She has taken six doses. Her immunizations are up to date. She is conscious, alert and complains of pain over the neck area. On examination she has pain on flexion of the neck. An LP showed 453 WBCs with 75% neutrophils and a glucose of 50 mg% (blood glucose 90 mg%) and a protein value of 55 mg%. A gram strain is negative for bacteria. Her headache improves and she appears less ill following the LP. She is admitted to the hospital with the diagnosis of viral meningitis. A repeat LP done 20 hours after the initial LP, shows 315 WBCs with 83% lymphocytes and a glucose value of 75 mg%, blood glucose of 89 mg%, and protein of 30 mg%. She is largely asymptomatic following the second LP. CSF cultures remain negative. A CSF PCR for enterovirus is positive.


Aseptic meningitis is characterized by lymphocytic/monocytic predominance of the CSF differential. The CSF protein is not as high and the glucose is not as low, compared to bacterial meningitis. Aseptic meningitis is almost always due to viral etiologies; however the rare case of tuberculous and fungal meningitis will present as an aseptic meningitis as well. Patients with viral meningitis can have all of the signs and symptoms of patients with bacterial meningitis; however, their findings are less severe. The classic patient with bacterial meningitis is toxic in appearance, irritable, and/or lethargic, possibly with other signs of sepsis. The typical patient with viral meningitis is alert and cooperative, but uncomfortable and mildly ill. Young infants are the most difficult to assess. Older cooperative children who can speak and express their symptoms are easier to evaluate. A lumbar puncture has two advantages in cases of viral meningitis in that it will usually ascertain a firm diagnosis and it will usually provide some degree of headache relief.

CSF neutrophil predominance can be initially seen in up to two thirds of cases of meningitis due to enterovirus and a slight decrease in the CSF blood glucose ratio occurs in one fourth of pediatric enteroviral meningitis. The low protein value and the relative low WBC are also indicative of a viral etiology. Enteroviruses are the leading cause of aseptic meningitis and account for 90 percent of all cases in which a pathogen is identified. Infants and children are most commonly affected and the prognosis is generally excellent. A CSF PCR for enterovirus is highly accurate in making an etiological diagnosis and will be positive in the great majority of cases. The repeated LP done 12 to 24 hours after the first will show a rapid shift in the CSF differential count from neutrophils to mononuclear predominance.


Questions

1. A three year old male presents with a bad headache, nausea, photophobia and fever (temp 38 degrees). His immunizations are up to date. He is not toxic in appearance. He is alert and cooperative. He has mild photophobia and mild nuchal discomfort without rigidity. He can speak and ambulate normally. The remainder of his exam is unremarkable. If this patient has meningitis, does he/she have bacterial or viral meningitis? What factors suggest one or the other?

2. An LP is done on the patient in question #1. The results show the following: 3 RBCs, 200 WBCs, 70% segs, 10% lymphs, 20 % monos, total protein 45, glucose 50. Gram stain of the CSF shows many WBCs and no organisms seen. Is this CSF analysis consistent with bacterial or viral meningitis? Which factors suggest one or the other?

3. What are the three most common bacteria that cause meningitis and what antibiotic covers them with close to 100% certainty?

4. Match the CSF results with the diagnosis (normal CSF, viral meningitis, bacterial meningitis). Validate your answer. Assume that the patient is 6 months old.

CSF 1
CSF 2
CSF 3
CSF 4
White cells
1243
5
190
250
% Neutrophils
94%
1%
60%
86%
CSF Glucose
23
65
50
47
Blood Glucose
78
85
87
90
Protein
62
21
48
49


References

Dodge PR. Neurological Sequela of acute bacterial meningitis. Pediatr Ann 1994;23:101-106.

Wubbel L, McCracken CH. Management of bacterial meningitis. Pediatr in Rev 1998;19:78-84.

Schuchat A, Robinson K, Wengor JD, et al. Bacterial meningitis in the United States, 1995. N Engl J Med 1997;337:970-976.

Feigin RD, Shackelford PG. Value of repeat lumbar puncture in the diagnosis of meningitis. N Engl J Med 1973;289:571-574.


Answers to questions

1. This is most likely a viral meningitis. He is older, so his risk of bacterial meningitis is lower. He has been fully immunized, which presumably means that he has had H. influenzae, type B vaccine. He has probably had pneumococcal vaccine, but this can't be automatically assumed. He is alert, ambulatory, and not toxic in appearance, which all suggest that he does not have an overwhelming infection such as bacterial meningitis.

2. This is most consistent with viral meningitis. Although he has a high percentage of segs, this is still consistent with early viral meningitis. Cases of bacterial meningitis which have not been pre-treated with antibiotics almost always have more than 90% segs. The gram stain does not show any organisms which makes bacterial meningitis less likely. This laboratory analysis of his CSF suggesting viral meningitis, is consistent with his clinical appearance which also suggests viral meningitis (see the answer to #1 above).

3. Pneumococcus, meningococcus and Haemophilus influenzae type B. Pneumococcus is usually sensitive to penicillins and cephalosporins, but some resistance has emerged so vancomycin should be given in addition to cefotaxime or ceftriaxone. Meningococcus is sensitive to penicillin so cefotaxime or ceftriaxone provides sufficient coverage. H. influenzae type B is sensitive to cefotaxime and ceftriaxone, but this organism is not a common cause of bacterial meningitis due to widespread immunization against this organism.

4. CSF 1 shows bacterial meningitis. The increased number of cells in the CSF with a predominant number of neutrophils makes this a strong likelihood possibility. In addition, he also has a very low glucose CSF level (CSF, blood glucose ratio of 25%) and an increased protein value sometimes. Cases of early viral meningitis can present with an increased number of cells and neutrophils but usually the CSF glucose is normal or not lower than 40% of the blood CSF value.

4. CSF 2 is normal. The normal number of WBCs in the CSF depends upon the age of the patient. The younger and more immature the infant is, the higher the value is. CSF glucose value depends upon the value of glucose in the blood and upon the integrity of the blood brain barrier. In patients with normal meninges the CSF value is usually about 75% of the blood level. When the meninges become inflamed, the active transport of glucose across the blood brain barrier becomes altered and the ratio drops proportionately to the degree of inflammation. Most viral meningitis produce less changes than bacterial meningitis accordingly CSF glucose values are lower in bacterial meningitis.

4. CSF 3 shows viral meningitis. Most cases of viral meningitis will present with a moderate increase in the number of white cells and a percentage of neutrophils not higher than 60-70%.

4. CSF 4 is inconclusive. The high percentage of neutrophils indicates that bacterial meningitis is possible. It would be wise to administer antibiotics until more information can be obtained. The gram stain result will be helpful. If it is positive for organisms, then this indicates bacterial meningitis. If the gram stain is negative, bacterial meningitis still cannot be totally ruled out. The child's clinical condition is not part of this table, but in reality, a child who is alert, active and playful is more likely to have viral meningitis, as opposed to a lethargic, toxic child who is more likely to have bacterial meningitis. This will probably turn out to be a case of viral meningitis despite the high percentage of neutrophils, since an early viral meningitis will often have high neutrophil percentages. A repeat LP 12 to 24 hours from the first LP will be helpful. A repeat LP which demonstrates a clear shift toward mononuclear cells, is consistent with viral meningitis, while no shift, or only a slight shift would suggest bacterial meningitis. Culture of the CSF will be most definitive if it is positive, but this result will not be available for at least 24 hours.


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