Meningitis

Meningitis: 
The meninges consist of three parts: the pia, arachnoid, and dura maters. Bacterial meningitis reflects infection of the arachnoid mater and the CSF in both the subarachnoid space and the cerebral ventricles.  
 
Etiology
Streptococcus pneumoniae, Neisseria meningitidis, and, less often, Haemophilus influenzae and group B streptococcus are the most likely causes of community-acquired bacterial meningitis in otherwise healthy adults up to the age of 60. Individuals over aged 50 years are also at increased risk of Listeria monocytogenes meningitis.  Psudomonas and Staph aureus is common in post CSF shunt and neurosurgical procedures. 
 
Clinical manifestations — The classic triad of acute bacterial meningitis consists of fever, nuchal rigidity, and a change in mental status, with or without headache. 
 
Neurologic complications such as seizures, focal neurologic deficits (including cranial nerve palsies), and papilledema may be present early or occur later in the course. N. meningitidis can cause characteristic skin manifestations, such as petechiae and palpable purpura. 
 
Kernig sign refers to the inability or reluctance to allow full extension of the knee when the hip is flexed 90 degrees. The classic Brudzinski sign refers to spontaneous flexion of the hips during attempted passive flexion of the neck. These signs are not reliable and highly operator dependant. ( Sensitivity for neck stiffness 31%, Brudzinski 9%, Kernig 11%). 
 
Laboratory studies — White blood cell count is usually elevated. The platelet count may also be reduced. Coagulation studies may be consistent with disseminated intravascular coagulation. Blood cultures are often positive and can be useful in the event that cerebrospinal fluid cannot be obtained before the administration of antimicrobials.  
 
Lumbar Puncture— Examination of the cerebrospinal fluid (CSF) is crucial for establishing the diagnosis of bacterial meningitis, identifying the causative organism.  CSF should be sent for gram stain, cell count, culture, glucose, protein and lactate. 
 
After lumbar puncture, there is normally a mild, transient lowering of lumbar CSF pressure as a result of removal of CSF and continued leakage of CSF from the opening made in the arachnoid membrane that is rapidly communicated throughout the subarachnoid space. In patients with intracranial, space-occupying lesions, there is a relative pressure gradient with downward displacement of the cerebrum and brainstem that can be increased by lumbar puncture, thereby precipitating brain herniation. 
 
A CT head to rule out mass lesion or raised ICP is not necessary in every patient before LP.  However, a CT head is indicated before LP in the following:  
  • Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic stem cell transplantation) 
  • History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection) 
  • New onset seizure (within one week of presentation) 
  • Papilledema 
  • Severe altered mental status
  • Focal neurologic deficits 
Normal CSF values are less than 50 mg/dL of protein, CSF/Serum glucose is >60% and less than 5 white blood cells/microL. Normal CSF opening pressure is less than 20cm Hg.  
 
Pleocytosis — It is important to note that a false-positive elevation of the CSF white blood cell (WBC) count can be found after traumatic lumbar puncture or in patients with intracerebral or subarachnoid hemorrhage in which both red blood cells and white blood cells are introduced into the subarachnoid space. A good rule of thumb for estimating the adjusted WBC count is to subtract one WBC for every 500 to 1500 red blood cells (RBCs) measured in the CSF. 
 
The usual CSF findings in patients with bacterial meningitis are a white blood cell count of 1000 to 5000/microL with neutrophils >80%, protein of 150 to 500 mg/dL, and glucose <40 mg/dL (with a CSF: Serum glucose ratio of ≤0.4). CSF protein may also be elevated in traumatic LP or SAH. 
 
CSF findings in viral meningitis include WBC less than 250, protein less than 150, glucose more than 50% of serum glucose. 
 
CSF lactate concentrations of > 4.2 mmol/L were considered to be a positive discriminative factor for bacterial meningitis, However, this test have utility only in post-op neurosurgical patients. Its value is very limited in patients who recieved antibiotics before lumbar puncture. 
 
CSF culture is positive in 60–90% of bacterial meningitis patients depending on the definition of bacterial meningitis. Pretreatment with antibiotics decreases the yield of CSF culture by 10–20%.
 
Treatment: 
  1. Antibiotics: Blood cultures and LP should be done before giving antibiotics. However, if they are to be delayed by more than an hour, antibiotics should be given. Similarly, antibiotics should not be delayed if imaging is to be done before LP. The regimen is  
  • Ceftriaxone 2gm Q12hrs or Cefepime 2gm Q8hrs or Meropenem 2gm Q8hrs. Avoid Imipenem due to risk of seizures but Meropenem is safe. In pencillin allergic patients, aztreonam and flouroquinolones can be considered. 
  • Vancomycin 15-20mg/kg every 8-12 hours not exceeding 2gm Q12hrs. Maintain Vanco trough of 15-20. Usually indicated in neurosurgical patients. 
  • Ampicillin 2gm Q4hrs for listeria. Bactrim is an alternative. 
  1. Decadron. 10mg Q6hrs for 4 days should be given before or at the same time of giving antibiotics, if suggestive of bacterial meningitis, especially pneumococcus (not viral meningitis). It showed mortality benefit. (NEJM 347:1549-1556). However, it should not be given if antibiotics are given more than 4 hours ago. Dexamethasone should only be continued if the CSF Gram stain and/or the CSF or blood cultures reveal S. pneumoniae. 
  2. All antibiotics can be discontinued if CSF cultures are negative for 48-72 hours. 
  3. The recommended treatment for bacterial meningitis patients in whom no pathogen can be cultured should be for a minimum duration of 2 weeks.
  4. Patients with bacterial meningitis who have elevations of intracranial pressure (ICP), and who are stuporous or comatose, may benefit from insertion of an ICP monitoring device. Methods to reduce ICP include elevating the head of the bed to 30º and hyperventilation to maintain PaCO2 between 27 and 30 mm Hg.  
  5. There is limited utility to routine repeat LP to assess the response to therapy in adults with bacterial meningitis. However, repeat LP is indicated if patient didn’t respond after 48 hours of antibiotics 
  6. Duration of treatment is 7 days for hemophillus/ nisseria menigitidis, 10-14 days for S.pneumoniae, 14 days for S.Aureus, 14-21 days for S.agalactiae, 21 days for listeria, 21 days for other gram negative bacilli like pseudomonas, E.coli and Klebsiella. 
 
PEARLS
  • Aseptic/Viral Meningitis: Clinical and lab evidence of meningitis with negative cultures. Most common cause is Entero virus. Others include coxsackie, malignancy, HIV, arbo virus, west nile virus and echo virus 
  • Viral meningitis usually has CSF pleocytosis with lymphocyte predominance. It is self limited.  
  • Hemorrhagic encephalidites, most notably herpes encephalitis, may result in a significant number of RBCs in the cell count of an otherwise atraumatic lumbar puncture and should suspect a viral etiology. In these cases, pending PCR results (where available) empiric therapy with acyclovir is warranted as this is the only treatment available to these patients. The usual dosage is 10 mg/kg every 8 hours. HSV meningitis can be treated with acyclovir for 10-14 days. 
  • Encephalitis: The presence or absence of normal brain function is the important distinguishing feature between encephalitis and meningitis. Patients with meningitis may be uncomfortable, lethargic, or distracted by headache, but their cerebral function remains normal. In encephalitis, however, abnormalities in brain function are expected, including altered mental status, motor or sensory deficits, altered behavior and personality changes, and speech or movement disorders.  Meningoencephalitis is also fairly common with symptoms of both. 
  • Normal CSF pressure is less than 20cm Hg in decubitus position. 
  • For immunocompromised patients, therapy should be expanded to cover for gram negative organisms, including Pseudomonas aeruginosa. Options for therapy in this situation include ampicillin and ceftazidime, or meropenem, with an aminoglycoside. 
  • Chemoprophylaxis for exposure to meningitis patients is by a single dose of CIPRO 500mg or zithromax 500mg. 
  • A normal CSF doesn’t always exclude the diagnosis of bacterial meningitis. Initial normal CSF might later yield a positive organism on culture. 
  • For CSF shunt infections, no antimicrobial agent has been approved by the US Food and Drug Administration for intraventricular use, and the specific indications are not welldefined.
 

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