Central Nervous System Infections

Neck stiffness (nuchal rigidity): 30% sensitivity, 68% specificity of adults.^10,11,12 In children, it is a bit less helpful, but occurs in 78% of children by the age of 2.

Brudzinski’s-when you flex the neck, pt must flex hips (both of these have 5% Sensitivity, 95% specificity) Clin Infect Dis 35:46, 2002

Jolt Maneuver-A more promising examination involves the "jolt maneuver." To perform this test, ask the patient to rapidly (2-3 times per second) shake his or her head from side to side. In one study, accentuation of the headache by this maneuver was 100% sensitive and 54% specific for meningitis; the study’s authors claim that the test is the most useful adjunctive maneuver for evaluating headache in the presence of fever. (Headache. 1991 Mar;31(3)) (JAMA 1999, 282:175)

The CBC should never be used to rule out meningitis; nearly one-third of patients with meningitis have a normal white count and differential

In the recent Canadian experience, CSF analyses of bacterial meningitis provide chilling data. Of 103 cases, only 56 had WBC counts greater than 1,000. 35% had counts from 100-1000, and a startling 10% had WBC counts under 100. All but one, however, had protein levels above 45, and 65% had levels of greater than 200.⁴ These cases represent primarily community acquired cases of meningitis in Alberta from 1985-1997. Of note, however, 43 out of a total of 103 patients had received previous antibiotics (Medicine. 79:6, 2000)

The CSF
lactic acid readily differentiates
bacterial (< 6 mmol/l), from partially
treated (4–6 mmol/l), from viral
meningitis (> 2 mmol/l),

Some would argue that differentiating between bacterial and viral by CSF parameters is a myth. Bacterial meningitis can exist within the range of viral parameters. (Can J Emerg Med 2003;5(5):348-9)

Normal CSF pressure ranges from 5-20 cm CSF or <200 mm CSF when the patient is in the usual decubitus position. Measuring the pressure may occasionally be helpful, as CSF pressures may be significantly elevated in a variety of headache conditions. These include SAH, CVT, bacterial and cryptococcal meningitis, and pseudotumor cerebri.

For certain special situations, other choices or additions may be appropriate. In the neonate and the elderly (>60 y.o.), the addition of ampicillin is warranted due to increased rates of infection with Listeria monocytogenes, enterococci, and Streptococcus agalactiae.¹⁹ 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.¹⁹ Finally, in those with a recent history of neurosurgery or in the presence of a shunt, extra attention should be directed to Staphylococcus aureus with the addition of oxacillin/nafcillin or vancomycin.¹⁹ If the patient has an altered mental status, focal neurologic signs, or seizures, herpetic encephalitis should be considered. Furthermore, 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 alert the EP to the presence of a possibly treatable 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 .²⁴

Dexamethasone is administered in a dose of 10 mg intravenously every six hours for four days and the regimen should be initiated before or with the first dose of antibiotics. Of note, vancomycin should not be used as the sole antibiotic in a patient with suspected pneumococcal meningitis who is receiving concomitant dexamethasone therapy, as there is the concern that a diminished CSF inflammatory response may substantially reduce vancomycin concentrations in cerebrospinal fluid and delay CSF sterilization.
References:
de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-1556.

Corticosteroids should be given as early as possible in all cases of ABM, using the published dose of dexamethasone, 10 mg every 6 hours in adults, or 0.4 to 0.6 mg/kg per d divided in 4 daily doses for children for 4 days. Ideally, dexamethasone should be administered before the antibiotics. (ACP Journal Club March/April 2004)

STEROIDS IN ADULTS WITH ACUTE BACTERIAL MENINGITIS: A SYSTEMATIC REVIEW
Lancet Infect Dis 4:139, March 2004
CONCLUSIONS: The authors feel that these findings support the use of adjunctive steroid treatment in adults with acute bacterial meningitis. They recommend a four-day course of IV dexamethasone (10mg every six hours), begun before or with the first dose of antibiotics, except in patients who are immunocompromised, are in septic shock, have already been treated with parenteral antibiotics, or have post-neurosurgical meningitis. 32 references

CHEMOPROPHYLAXIS OF MENINGOCOCCAL AND HiB MENINGITIS

Chemoprophylaxis Against Meningococcal Disease - Who Needs It?

When an Emergency Physician identifies a case of meningococcal disease, the patient's close contacts must be prescribed an effective antimicrobial agent to eradicate potential colonization by N. meningitidis. Frequently, an overreaction ensues regarding who actually needs to be treated.

The definition of "close contact" is not precise, but it is intended to include persons who have had prolonged (> 8 hours) contact while in close proximity (3 ft is the general limit for large-droplet spread) to the patient or who have been directly exposed to the patient's oral secretions (e.g., through prolonged face-to-face contact, mouth-to-mouth resuscitation, kissing, or management of an endotracheal tube) within 1 week before the onset of the patient's symptoms until 24 hours after appropriate antimicrobial therapy has been initiated. Such persons typically include members of the household and roommates, persons at a child-care center, and others who have had prolonged exposure to the infected patient (e.g., travelers on an airplane seated next to the patient for more than 8 hours) (1,2). Classmates and coworkers are not included unless they meet the criteria for close contact. Close contacts who have previously received meningococcal vaccination should still be given chemoprophylaxis, because the vaccines do not confer 100% protection and immunity wanes with time.

Ideally, chemoprophylaxis should be started within 24 hours after the index case has been identified, although diminishing levels of benefit may still be realized even with delays of up to 2 weeks (1,3).

References:
(1) Gardner P. Prevention of Meningococcal Disease NEJM 2006; 355:1466-1473.
(2) Guidelines for the management of airline passengers exposed to meningococcal disease. Atlanta:Centers for Disease Control and Prevention, 2000 (http://www.cdc.gov).
(3) Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2005;54:1-21.

Initial Tap-negative Meningitis

It is a popular misconception that a normal CSF excludes the diagnosis of bacterial meningitis. However, our case, and others reported in the literature, demonstrate that an initial ‘normal’ CSF might later yield a positive organism on culture. A normal CSF is defined as less than 5 white cells per cubic millimetre, with no more than 1 polymorphonuclear cells, glucose level greater than 40% of the serum glucose concentration, less than 45 mg/dL of protein and a negative Gram stain. In a study by Polk and Steele of 261 patients from a large paediatric hospital over a 6 year period, 7 (2.7%) had a positive CSF culture despite initially normal CSF parameters.² This report also found that the spectrum of the patients' ages and the recovered pathogen was rather varied. Another study of 82 patients with documented meningococcal meningitis reported that 8 (9.7%) initially had normal CSF results.³ None had received previous antibiotic treatment. Other authors have reported that meningitis with an initially normal CSF accounts for 0.5% to 12% of all cases of bacterial meningitis.³ The causative organisms are usually common meningeal pathogens (N. meningitidis, H. influenzae and S. pneumoniae),³ although other organisms causing a similar clinical picture have been described (P. mirabilis, group B Streptoccus).^2,4

^{1.

Van de Beek D, De Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M.
Clinical features and prognostic factors in adults with bacterial meningitis. N
Engl. J. Med. 2004; 351: 1849–59.

CrossRef, Medline, ISI

2.

Polk DB, Steele RW. Bacterial meningitis presenting with normal cerebrospinal
fluid. Pediatr. Infect. Dis. J. 1987; 6: 1040–42.

3.

Coll M, Uriz M, Pineda V et al. Meningococcal meningitis with ‘normal’
cerebrospinal fluid. J. Infect. 1994; 29: 289–94.

CrossRef, Medline, ISI, CSA

4.

Onorato IM, Wormser GP, Nicholas P. ‘Normal’ CSF in bacterial meningitis. JAMA
1980; 244: 1469–71.

CrossRef, Medline, ISI}

Brain Abscess

Can be due to bacteria, fungi, or protozoa. Usually from direct extension, such as sinusitis, but also may be from large bacteremia.

Patients may present without fever, without white count. LP will be negative and may be dangerous.

Usually anaerobic, strep, enterobacteriaceae, and staph are the most common aerobes.

Pseudomonas pseudomallei, which produces discrete abscesses like this and which is endemic in Southeast Asia. They often present as focal seizures.

Hereditary Hemorrhagic Telangiectasia (HHT) or Osler-Weber-Rendu: autosomal dominant. Telangiectasias and AVMs in lungs, liver GI, and brain. Triad of telangiectasias, recurrent epistaxis, and family history. Pulmonary AVMs allow for paradoxical embolisms. Brain abscess from septic emboli

Encephalitis

Viral encephalitis is usually called by arbovirus or a herpes virus

Herpes Virus Encephalitis is caused by HSV-1, Varicella, Epstein-Barr, or CMV.

With a sensitivity and specificity > than 95%, PCR testing of CSF for herpes viruses is considered the criterion standard for diagnosing herpes virus meningitis/encephalitis (Mayo Clin Proc, 12/107, pg. 1562).emedhome

Acute Disseminated Encephalomyelitis (ADEM) is an autoimmune disorder that occurs several weeks after a viral illness. It is probably the cause of up to 1/3 of viral encephalitis.

The most common arboviruses are St. Louis and West Nile.

Since disseminated by arthopod vector, predominate in warm summer months

CTs are negative, MRI will show changes in HSV

Virus testing of the CSF can be done with PCR.

Acyclovir improves HSV encephalitis, probably not helpful in West Nile.

West Nile

A disease of mosquitoes and birds. Human to human transmission has only been documented with blood transfusions. The transfusions and mosquitoes are the only known vectors for the disease.

Incubation is 3 to 14 days

Onset of the infection is West Nile Fever: syndrome of fever, myalgias, headache, and GI symptoms. Maculopapular rashes are occasionally noted as well.

Most people will produce IgM and clear the virus without further progression.

In some, the virus will cross the BBB and a meningoencephalitis will develop.

The damage is most consistently to the brainstem.

It will present with fever, headache, and possibly, decreased DTR, muscular weakness sometimes with flaccid paralysis, and respiratory compromise.

CSF will usually demonstrate pleocytosis, lymphocyte predominance, increased protein, and normal glucose.

An elisa for IgM is available.

Herpes

temporal or parietal abnormalities on CT or MRI.

Untreated mortality rate of ~80%

CSF shoes pleocytosis with polys or lymphocytes

RBCs are usually present

Need CSF PCR

Most cases are from HSV-1 but HSV-2 is also seen

consider syphyllis in the diagnosis

The human herpesvirus (HHV) family, also known as herpes simplex virus (HSV), includes two clinically important strains. Herpes simplex virus type 1 (HSV-1) typically causes oral lesions, while herpes simplex virus type 2 (HSV-2) usually causes genital lesions. Both strains also may be associated with encephalitis, commonly called herpes simplex encephalitis (HSE). HSV-1 is more commonly implicated in adult encephalitis, while HSV-2 more typically causes newborn encephalitis through spread from the maternal genital tract [1, 2 and 3].

Herpes simplex encephalitis is the most common cause of sporadic viral encephalitis, accounting for approximately two cases per million persons per year in the United States [1 and 4]. The disease affects men and women equally and has no seasonal variability. Approximately one-third of cases develop in patients under 20 years of age and one-half in patients over 50 years [1 and 2].

Symptoms of HSE are variable. Patients often will have a prodrome of malaise, fever, headache, and nausea. This prodrome is followed by the onset of either acute or subacute encephalopathy, typically manifested by lethargy, confusion, delirium, personality change, or even coma. Focal neurological deficits are common, with seizure, ataxia, hemiparesis, and dysphasia all typical findings. Physical examination of patients with HSE is also variable. The neurological examination may be completely normal or can reveal focal or generalized deficits [1, 2, 4 and 5]. Additionally, the absence of nuchal rigidity is suggestive of encephalitis as opposed to meningitis [1].

In suspected cases of HSE, the work-up must be initiated rapidly, although treatment should not be delayed while making the diagnosis. Neurodiagnostic tests that can support a presumptive diagnosis of HSE include brain CT or MRI scanning, CSF analysis, EEG, and historically, brain biopsy.

Imaging studies are often helpful in making the diagnosis, but may be more useful in ruling out other pathology. The CT scan of the head may show low-density lesions, especially in the temporal lobes. However, these lesions are only present in two-thirds of cases and may not appear until 3 to 4 days after symptom onset [2]. The MRI is more accurate than a CT scan and is now considered the imaging study of choice in suspected cases of HSE. Pathologic changes in the infero-medial portion of the temporal lobes are most commonly displayed on T2 hyper-intensity images and are highly suggestive of HSE [2 and 6].

Additional investigation should include a lumbar puncture, once a space-occupying lesion has been ruled out by imaging studies. Common lumbar puncture results include a mononuclear pleocytosis with mildly elevated protein and normal glucose [1 and 2]. Also, because of the hemorrhagic nature of the infectious process, red blood cells and xanthochromia are commonly seen, but are not diagnostic. A small percentage of patients will have completely normal CSF.

The HSV virus only rarely can be cultured from CSF. As a result, PCR analysis of the CSF is the preferred diagnostic test in HSE as it is highly sensitive and specific in making the diagnosis and will remain positive up to 5 days after the initiation of antiviral therapy [2, 3 and 7].

Electroencephalography (EEG) can be of value in confirming the diagnosis of HSE. Characteristic periodic high-voltage spike wave activity emanating from the temporal lobes and slow wave complexes are highly suggestive of HSE. These findings are present in four-fifths of biopsy-proven cases of HSE, and have a sensitivity of 84% and specificity of 33% [1 and 2].

Historically, brain biopsy was considered the only definitive means of diagnosing HSE [1]. However, since the advent of PCR analysis of CSF, the role of biopsy has markedly diminished.

Standard pharmacotherapy for HSE is intravenous Acyclovir at a dose of 10 mg/kg every 8 h, with dose adjustment for renal insufficiency. Acyclovir has completely supplanted Vidarabine, which is less effective and more toxic [8]. Intravenous Acyclovir should be initiated as soon as the diagnosis of HSE is suspected rather than delayed until the diagnosis is confirmed; delayed initiation of Acyclovir treatment for more than 2 days after hospital admission is associated with poor outcomes [9].

HSE is progressive and often is fatal in 7 to 14 days if not treated. A landmark study by Whitley et al. in 1977 reported a 70% mortality rate in untreated patients and severe neurological deficits in most survivors [1 and 4]. Even in treated cases of HSE, the mortality rate is still high, while complications and neurological sequelae are also common [10].

Herpes simplex virus infection of the brain is the only viral CNS infection for which therapy has been proven useful in controlled trials. Successful therapy depends on considering the possibility of the disease and the early institution of antiviral therapy. The presence of CSF pleocytosis and elevated protein in a patient with encephalopathy in the absence of identifiable pathogens should be considered due to HSV until proven otherwise.
(JEM 2004, 26:1)

*CSF Findings*	*WBCs*	*Glucose*	*Protein*	*Main Cells*	*Lactate*
Bacterial	5 to 1000	0 to 45	15 to 45	PMNs	>6
Viral	5 to 2000	Normal	20 to 200	Lymphs	2-4
TB	5 to 500	10 to 45	45 to 500	Lymphs
Normal	0 to 5	45 to 80	15 to 45	Monos	<2