History Part 3: Competing diagnoses that can mimic brain abscess.

 Other infectious processes (imaging will help differentiate)

o Meningitis

o Viral encephalitis

o Subdural empyema

o Neurocysticercosis

 Inflammatory processes

o Multiple sclerosis

o Neuromyelitis optica

o Differentiating factors:

o Cultures are negative

o Can have positive oligoclonal bands and immunoglobulin G (IgG) index

o Patients usually have previous events (numbness, tingling, weakness, visual loss, etc.) that
can be elicited by a thorough history

o No fever

 Malignancy

o Glioma

o Lymphoma

o Differentiating factors:

o Negative cultures

o Positive flow cytometry or cytology

o B-type symptoms

o Duration is generally longer prior to presentation

 Intraparenchymal hematoma

o Resolving hematomas can have a similar appearance on magnetic resonance imaging

(MRI)

o Differentiating factors:

o Negative cultures

o Neuroimaging features change with time consistent with intraparenchymal hematoma

o History of risk factors for intraparenchymal hematoma

 Contusion

o Differentiating factors:

o Negative cultures

o History of trauma

 Ischemia

o Subacute ischemia can have contrast enhancement, but not in the same pattern. Restricted
diffusion may or may not be present.

 Radiation necrosis

o Differentiating factors:

o Negative cultures

o History of radiation

D. Physical Examination Findings.

 Neurological findings are dependent upon the location and size of the lesion. In some
cases, consciousness can be mildly impaired and no focal deficits can be ascertained.

 Frontal lobe: poor attention, decline in cognitive abilities, hemiparesis, and seizures.

 Temporal lobe: aphasia, visual field deficits, hemiparesis or sensory deficits, particularly in
the face.

 Parietal lobe: findings can be subtle, but can include neglect and apraxia.

 Occipital lobe: homonymous hemianopia.

 Cerebellar: ataxia, nystagmus, spasticity, and increased reflexes. Impaired consciousness

due to compression of fourth ventricle leading to hydrocephalus can occur.

 Basal ganglia: movement disorders (hemiballismus, etc.).

 Multiple lesions: difficult to localize physical examination signs.

E. What diagnostic tests should be performed?

The physical examination findings in brain abscess can be highly varied and are dependent
upon the size and location of the abscess. A search for the source of the lesion should be
performed during the physical examination.

 Full neurological examination

o Focal findings can help localize the lesion, but focal findings may not be present in all
cases.

 Fundoscopic examination

o Evaluate for papilledema and Roth spots

 Otoscopic examination: fluid levels; appearance of tympanic membrane can help diagnose
otitis media.

 General examination

o Evaluate periphery for Janeway lesions

o Heart murmur can also help identify endocarditis

 Dental examination: The initial examination does not need to be performed by a dentist; a
thorough visual inspection can be performed. If strong suspicion remains for a dental source
and initial examination is negative, then a referral to dentistry would be appropriate.

1. What laboratory studies (if any) should be ordered to help establish the
diagnosis? How should the results be interpreted?
 Complete blood count (CBC): elevated white count.

 Blood cultures: positive in approximately 10% of cases.

 Lumbar puncture: Prior to performing the procedure, perform imaging to ensure that
vasogenic edema has not caused significant mass effect, and risk of herniation is low.
Positive in 10-30% of cases. Cerebrospinal fluid (CSF) can be normal if abscess is
localized. Intracranial pressure is usually 20 to 300 millimeters mercury (mmHg). White cell
count is usually elevated in brain abscess. Cell count ranges from 0 to 100,000 cells per
microliter. Differential can help determine if the cause is more likely to be from bacterial or
fungal sources. If glucose is low, indicative of infectious process but is generally normal.

 Cytology and flow cytometry: helps to differentiate infection from malignancy.

 Erythrocyte sedimentation rate/C-reactive protein (ESR/CRP): non-specific, but likely to be

elevated in cases of brain abscess. CRP is more likely to be elevated than ESR.

 Human immunodeficiency virus (HIV): CD4 (cluster of differentiation 4) count in known HIV-
positive individuals.

 Any material obtained from a neurosurgical procedure should be sent to the laboratory for
pathological evaluation and cultures (aerobic, anaerobic, mycobacterial, fungal).

2. What imaging studies (if any) should be ordered to help establish the
diagnosis? How should the results be interpreted?
 Brain imaging is essential to the work-up of a patient with a suspected brain abscess.
Computed tomography (CT) and/or MRI with contrast should be performed. MRI is
preferred.

o CT shows enhancement of capsule. Hypodensity surrounding the capsule indicates edema.

o MRI

o T1 weighted images with contrast also show enhancement of capsule. May show a
characteristic "ring-enhancing lesion". Hypointensity is present in the necrotic core. Figure
1 is a typical "ring enhancing lesion" in a HIV-positive patient with toxoplasmosis. Figure 2 is
 an irregularly shaped capsule with enhancement in an immunosuppressed patient
with Listeria abscess.
o T2 and fluid-attenuated inversion recovery (FLAIR) images show hyperintense vasogenic
edema with hypointense capsule. Figure 3 shows FLAIR imaging in the HIV-positive patient
with toxoplasmosis.

o Diffusion weighted images (DWI) and apparent diffusion coefficient (ADC) images are
compared to help differentiate abscess from malignancy. Abscess usually has restricted
diffusion (brightness on DWI with correlating dark area on ADC). Figure 4 shows a central
area of restricted diffusion in the patient with Listeria abscess.
 Chest X-ray: evaluation of pulmonary causes.

 Echocardiogram: performed to evaluate for endocarditis.

o If a strong suspicion for endocarditis remains after a negative transthoracic

echocardiogram, then consider a transesophageal echocardiogram.

Figure 1.
T1 with contrast in a patient with toxoplasmosis
Figure 2.
T1 with contrast. Atypical appearance of abscess in immunocompromised patient. Listeria was
determined to be cause of abscess after contaminated cantelope ingestion.
Figure 3.
T2 FLAIR image in a HIV positive patient with toxoplasmosis
Figure 4.
Central area of restricted diffusion on DWI (left) and ADC (right) images. Immunocompromised
patient with multiple listeria abscesses.
F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
N/A

III. Default Management.

Management of brain abscess hinges upon correct antimicrobial treatment. Consultation
with an infectious disease specialist is recommended.
 Empiric treatment with third- or fourth-generation cephalosporin, vancomycin and
metronidazole is recommended until a source or organism can be identified.

 If contiguous spread from parameningeal foci (otitis media, mastoiditis, sinusitis):

ceftriaxone plus metronidazole. Vancomycin should be added if staphylococcal infection
suspected.

 History of penetrating trauma or neurosurgery: vancomycin plus third or fourth-generation

cephalosporin with anti-pseudomonal activity (e.g. cefepime) plus metronidazole.

 Treatment in HIV-positive patients should cover toxoplasmosis. Pyrimethamine and

sulfadiazine combination is a first line option for toxoplasmosis.

 Listeria abscess in immunocompromised patients should be considered. Ampicillin is the

treatment of choice.
 Once the infecting pathogen has been determined, antimicrobial agents can be modified to
achieve the most effective therapy. However, if the infection spread from a contiguous site,
broad spectrum antimicrobial therapy (including anaerobes) is recommended even if a
single organism is recovered in cultures.

Surgical management involves the following:

 Abscess aspiration can help to determine pathogen and to reduce the size of the abscess.
With modern stereotactic neurosurgical techniques, brain abscesses measuring at least 1
centimeter (cm) in diameter are amenable to stereotactic aspiration.

 An abscess size of 2.5 cm in diameter has been recommended as an indication for

neurosurgical intervention.

 If there is brain shift, with risk of brain herniation, neurosurgical intervention is indicated
regardless of abscess size.

 In patients with multiple abscesses, the largest abscess should be aspirated for diagnostic
purposes.

 Total resection has a limited role these days but if is considered when abscess is superficial
and not located in eloquent brain tissue and when there is suspicion of fungal or
tuberculous infection or of branching bacteria (Actinomyces or Nocardia).
 If edema is present causing hydrocephalus, shunting may be necessary.

Vasogenic edema may need to be treated if it is causing mass effect:

 High dose corticosteroids, such as dexamethasone, can be tapered over the course of
several days.

 If edema is severe and causing significant mass effect, mannitol or hypertonic saline can be
considered.

Seizure management involves the following:

 Patients with seizures should be placed on an antiepileptic. Phenytoin is a common choice

due to ease of administration and ability to check levels. Levetiracetam has become popular
due to minimal drug interactions and a more favorable side effect profile. Physicians should
be aware that despite frequent use of levetiracetam as monotherapy, Food and Drug
Administration (FDA) approval is for adjunct therapy. Prophylactic antiepileptic drugs in
patients with brain abscess are not routinely indicated.

A. Immediate management.
Antibiotics should be initiated as soon as possible. If mass effect is present, consider
corticosteroids. It is unusual to require an emergent neurosurgical procedure for abscess,
but a consultation should be considered if the patient has severe mass effect, is comatose,
stuporous or has a capsule larger than 2 cm.

B. Physical Examination Tips to Guide Management.

The neurological checks should be performed frequently by nursing, at least every 4 hours
after admission. Daily examinations should include a complete neurological examination to
evaluate for progression of symptoms, and should specifically be focused on symptoms that
localize near the lesion. For example, if a patient has an occipital lesion, visual fields should
be performed daily. If progression of symptoms occurs, such as progression of a
quadrantanopia to homonymous hemianopia, repeat imaging should be performed.

C. Laboratory Tests to Monitor Response To, and Adjustments in,

Management.
Drug levels of antibiotics should be monitored when appropriate (i.e. vancomycin).

Kidney function (creatinine) should be evaluated in patients on vancomycin.

If phenytoin is used, levels should be drawn daily until a clear therapeutic steady state is
achieved. Liver profiles should be checked at the onset of therapy, and approximately
weekly while the patient is admitted. If liver panels are not elevated in subsequent lab
draws, then infrequent intermittent checks should be performed.
D. Long-term management.
The length of intravenous antibiotic course is dependent upon the organism(s) found, but is
typically 6 to 8 weeks. This is often followed by oral antimicrobial therapy for 2 to 3 months if
an appropriate agent is available although the efficacy of this approach has not been
established. It is important to continue antibiotic therapy until resolution of the abscess by
neuroimaging. Of note, prolonged therapy with metronidazole can lead to peripheral
neuropathy.

Other consultations may be necessary, such as with oncology in a patient with cancer, or
cardiology in a patient with endocarditis. In patients with immunocompromised states,
careful coordination with consultants is required to ensure that medications are managed
appropriately.

Discontinuation of antiepileptics is controversial. Some patients require life-long treatment

and others can tolerate discontinuation of anti-epileptics if they have been seizure free for
more than 2 years. A consultation with a neurologist is recommended.

CT scans or MRI should be obtained to evaluate response to treatment. A repeat scan

should be considered within 2 weeks of starting treatment; a scan should be obtained
earlier if the patient is not responding to the therapy or develops new symptoms. When
discontinuation of antibiotics is reasonable, MRI should be obtained to evaluate for
resolution of the abscess. If the abscess enlarges after 2 weeks of antimicrobial therapy, or
fails to resolve after 3-4 weeks, further surgical aspiration or excision should be considered.

The combination of surgical aspiration or removal of all abscesses larger than 2.5 cm in
diameter, a 6-week or longer course of intravenous antibiotic therapy, and neuroimaging
follow-up until resolution provides the best chances for cure.

E. Common Pitfalls and Side-Effects of Management

Due to the non-specific symptoms that may accompany brain abscess, the diagnosis may
be delayed.

Antibiotics should be instituted as soon as possible. An aggressive work-up for a primary

source of infection is necessary. Antibiotics should be tailored to the source when possible
to reduce adverse effects. Antibiotics can be started prior to a lumbar puncture or
neurosurgical procedure if these get delayed.

Patients with intracranial abscess should be monitored closely for progression of disease.
Abscess rupture is an uncommon complication, but should be on the differential if a patient
worsens. Ventriculitis and diffuse spread of bacteria are associated with worse outcomes.

IV. Management with Co-Morbidities

N/A

A. Renal Insufficiency.
Dose reduction of antibiotics may be necessary.

Renally cleared antiepileptics (levetiracetam, topiramate, etc.) may require dose reduction.

B. Liver Insufficiency.
Drug levels of antiepileptics metabolized by the liver (phenytoin, valproate) should be
monitored. Liver function tests to ensure the values remain stable should be performed.

C. Systolic and Diastolic Heart Failure

Patients with brain abscess are frequently dehydrated due to poor intake, nausea and
vomiting. Careful replacement of fluids should occur in patients with heart failure.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in standard management.

E. Diabetes or other Endocrine issues

No change in standard management.

F. Malignancy
In patients with malignancy, a discussion should occur with the treating oncologist to
determine an appropriate treatment plan. Frequently, chemotherapeutics and radiation
treatments will be suspended during the treatment for brain abscess. A conversation with
the patient and the family regarding the consequences of deferment of treatment should
occur. In some cases, goals of care should be clearly established due to the consequences
of holding cancer treatment and neurological sequelae that can occur after abscess
treatment is complete.

G. Immunosuppression (HIV, chronic steroids, etc.).

Patients on immunosuppression for chronic diseases should consider a suspension of the
immunosuppressant. Coordination with the treating physician or a consultant should occur.
Several medications, such as azathioprine, will continue to cause immunosuppression for a
substantial amount of time after discontinuation of the medication. Unusual causes of brain
abscess (listeriosis, toxoplasmosis, etc.) should be considered, and antibiotics tailored
appropriately.
In patients with HIV with positive Toxoplasma IgG, low CD4 count and brain imaging
suspicious for abscess, treatment for toxoplasmosis should be started.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management.

I. Gastrointestinal or Nutrition Issues

No change in standard management.

J. Hematologic or Coagulation Issues

If endocarditis is a likely source of brain abscess, then vascular imaging should be
considered. Mycotic aneurysms can be identified on a CT angiogram or magnetic
resonance angiogram (MRA). Mycotic aneurysms have a risk of rupture with
anticoagulation. The risk-benefit ratio must be obtained in patients found to have a brain
abscess and an indication for anticoagulation.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

If the patient experiences focal neurological change, a CT scan should be immediately
obtained to evaluate for mass effect. Contrast could be considered if rupture of the abscess
is possible. Signs of rupture include severe headache, neck stiffness and altered mental
status.

Fever despite tailored antibiotics to the source of the infection should be further evaluated
with chest x-ray, blood cultures, urinalysis, and testing for Clostridium difficile if diarrhea is
present. Broadening the antibiotic regimen may be necessary if it is believed that the fever
originated from the abscess and is possibly improperly covered by the current antibiotic
regimen.

Antiepileptics should be started immediately in any patient who develops a seizure.

Phenytoin can be loaded at 20 milligrams/kilogram (mg/kg), maintained with 5mg/kg
(divided into twice a day dosing if greater than 300mg per dose) and monitored with daily
levels until a steady state is achieved. It may be necessary to monitor free levels in patients
with low albumin.
 B. Anticipated Length of Stay.
Length of stay is variable and is highly dependent upon severity of disease.

C. When is the Patient Ready for Discharge.

The patient is ready for discharge once the appropriate antibiotics have been chosen and
the patient is improving. Fever should be resolved, and symptomatic management should
properly treat headache, nausea and vomiting.

D. Arranging for Clinic Follow-up

1. When should clinic follow up be arranged and with whom.

 Primary care physician: within 1-2 weeks after discharge.

 Infectious disease: within 4-6 weeks after discharge and thereafter until discontinuation of
antibiotics.

 Neurosurgery: within 1-2 weeks.

 Neurology (if seizures or focal neurological deficits): within 6-8 weeks.

 Other specialists as indicated by the patient's course (oncology, cardiology, etc.).

2. What tests should be conducted prior to discharge to enable best clinic first
visit.
None

3. What tests should be ordered as an outpatient prior to, or on the day of, the
clinic visit.
CT or MRI with contrast to ensure resolution of abscess.

E. Placement Considerations.
Frequently, patients with brain abscess will require rehabilitation. Most patients require
acute or sub-acute rehabilitation. Rehabilitation specialties (physical, occupational and
speech therapy) should be consulted early during the hospitalization. A physical medicine
and rehabilitation physician can help to determine when the patient is stable for transfer to
these facilities based upon progress with therapy. This consultation should occur a few days
prior to the anticipated discharge.
 A peripherally inserted central catheter (PICC) line should be placed in all patients requiring
an outpatient course of intravenous antibiotics.

F. Prognosis and Patient Counseling.

Mortality due to brain abscess is approximately 15%. In subgroups, such as those with
immunosuppression after transplantation, deep or brainstem abscess, mortality can be as
high as 80%. Residual neurological deficits can be found in 30 to 55% of patients. Severe
neurological deficits can be present in 18%. Seizures usually occur within the first year after
diagnosis of brain abscess.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

 Deep vein thrombosis (DVT) prophylaxis

 Gastrointestinal (GI) prophylaxis with a proton pump inhibitor if steroids are used. Blood
sugar monitoring and an insulin sliding scale can also be considered with steroid use.

 If HIV-positive and low CD4, immune reconstitution with combined antiretroviral therapy is
recommended.