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Introduction References Case
Outcome Annotated
Bibliography Questions Headache and Inability to Solve Quadratic Equations Case Presentation A 32-year old man presents to the ED complaining of 3 weeks of headache (HA) and difficulty with his work. He is a mathematics graduate student in a PhD program at MIT, and he is concerned because during the 3 week period that he has had the HA, he has noticed that his ability to solve quadratic equations, and perform simple differential calculus problems has become worse. Both the HA and the math difficulties began about 3 weeks ago, gradual onset and have increased gradually since then. The HA is 7/10 in severity, gradual in onset and has waxed and waned over the 3 weeks. He rarely gets HA's and this one is unfamiliar in quality, and feels "like a pressure" over his left fronto-parietal area without radiation. He has tried extra-strength Tylenol with "about 66.67% improvement." He has noted nausea and vomited once the day before you see him. He denies neck pain or stiffness, fevers, chills, diplopia or changes in visual acuity, and weakness or numbness. The remainder of his ROS is negative, including no symptoms referable to the ears, sinuses, and respiratory, gastrointestinal or cardiovascular systems. There is no history of head trauma. His PHM is only noteworthy for mild asthma (never hospitalized, not on regular meds). He has no allergies. He does not smoke, and drinks socially (2-3 drinks per week). He is homosexual and has been in a monogamous relationship for 4 years. He tested negative for HIV a year ago. He is in the middle of defending his PhD thesis and has been having "philosophical differences of opinion" with his advisor. A diagnostic
study was performed in the ED.
Introduction Key Clinical Questions
Bacterial Brain Abscess Background, Risk Factors and Epidemiology Prior to the routine use of antibiotics for infections of the ears, sinuses, teeth and heart valves, bacterial brain abscess was a much more common disease than it is in 2003. Before 1900, brain abscess was almost always fatal, the diagnosis made at autopsy. In the late 1800s, the English surgeon William Macewan began treating these patients surgically, with has remained a mainstay of treatment to the present day. The nearly universal availability of CT scanning has revolutionized diagnosis of this condition and improvements in surgical techniques and the introduction of antibiotics has made an enormous impact on treatment. Currently the mortality rate has become markedly reduced.
Brain abscess is a focal, intracerebral infection that can be due to bacteria, fungi and protozoa. The blood-brain barrier (BBB) is relatively resistant to penetration of these microorganisms from the blood into the brain, which accounts for the relative rarity of this condition, despite the frequency of bacteremia. In fact, researchers must directly inoculate experimental animals to produce brain abscess because production of an abscess from intravenous placement of bacteria usually does not lead to abscess formation. In patients, the abscess will occasionally form in an abnormal area of brain (infarction, tumor or hematoma); however most develop in areas of previously normal brain tissue. Bacteria can
gain access to the CNS from direct extension of a contiguous infection
(e.g., sinusitis), from transit though the valveless emissary veins
into the intra-cranial venous system, from direct penetration (e.g.,
post-surgical or penetrating trauma), from bacteremia (see above). In
20-30% of cases of brain abscess, none of these mechanisms is identified,
leading to the so-called "cryptogenic abscess". Once the microorganism has penetrated the BBB, there is a well-defined evolution of pathological changes, as listed below:
The location can be anywhere in the head, and is often a clue as to the pathogenesis. For example, when the focus is the paranasal sinuses, frontal lobe abscesses are more common. Otogenic infections usually create temporal lobe and cerebellar abscesses. When bacteremia is the source, the infection can develop anywhere, but most commonly in the middle cerebral artery territory and often with multiple abscesses. When the cause is due to penetrating trauma or post-neurosurgery, the location is related variable. As well, the microbial flora tend to portend the source (see chart below).
(Chart adapted
from reference 1)
Most patients who are able to give a cogent history complain of HA. There is nothing in the details of the HA that distinguish one from a brain abscess from the myriad of other causes of HA. Abrupt onset suggests another diagnosis. Sometimes, abrupt worsening will occur with rupture of a brain abscess into a ventricle, but this complication is usually fatal and is associated with a severely ill patient. Seizures may occur, as well as symptoms of raised ICP (drowsiness, nausea and vomiting, lethargy and stupor). Fever is by no means universal being present in less than 50% of cases. In one series, while 50% had a history of fever, only 25% had documented fever on presentation. Focal neurological signs (hemi-motor or sensory symptoms, ataxia and aphasia) occur in 35-50% of cases and will depend entirely on where the abscess is located. Cerebellar abscesses are usually associated with ataxia and dizziness. Brainstem abscesses are usually associated with cranial nerve findings. Note that in patients with frontal lobe masses, even relatively large ones, the physical exam is often quite insensitive. These patients frequently will complain of "soft", odd sorts of symptoms that they are aware of, but that are difficult if not impossible to test. Papilledema
is found in 25% of patients with brain abscess. Findings suggestive
of a source from HEENT infection, endocarditis or other bacteremia may
be found in variable amounts of patients. Unfortunately, in the absence
of focal neurological findings or changes in mental status, there is
little to specifically suggest the diagnosis, which accounts for the
frequency with which the diagnosis is initially missed.
Standard laboratory testing is rarely helpful. The WBC count is often normal, and the ESR, while usually elevated, can be normal, and is not a standard ED test for patients with HA unless temporal arteritis is suspected. Blood cultures, while usually negative, should be obtained. Performing a lumbar puncture is not recommended if brain abscess if being considered. This is one condition in which transtentorial herniation has been reported, and more importantly, the CSF analysis is rarely diagnostically useful. The findings range from normal, for deep-seated abscesses, to non-specifically abnormal (elevated protein and pleocytosis) in most, to diagnostic in the extraordinary patient with either ventricular rupture or ventriculitis from adjacent pus. In these latter patients, LP would likely be clinically contraindicated. At surgery,
or at stereotactic brain biopsy, pus is cultured. This is vitally important
since the course of therapy often lasts for 6-8 weeks and is parenteral.
This is obviously not done in the ED, but with modern microbiological
techniques, the organism is almost always isolated.
CT and MR have completely revolutionized the diagnosis of brain abscess. The four pathological stages can be seen radiographically. The earliest stages of cerebritis will usually show some vasogenic edema (black on non-contrast CT). It is worth mentioning brain abscess to the radiologist, since contrast will often be administered. As well, sometimes repeat images taken 30-60 minutes after contrast injection, will sometimes clarify an early cerebritis. By MR, T-1 imaging, edema appears hypo-intense (black), while on T-2 imaging, the edema appears white. Later on in the patient's course, repeated imaging is used to follow the response to therapy. It is also important to recall that a ring-enhancing lesion by CT has a differential diagnosis that includes tumor (both primary brain, metastatic and lymphoma), necrotizing encephalitis, infarction, granuloma, as well as abscess due to toxoplasmosis and fungi. If brain abscess is high in the differential diagnosis, MR is preferable to CT when it is available. More advanced
imaging studies are sometimes performed but are rarely if ever necessary
in the ED.
As mentioned above, LP is potentially dangerous and notoriously non-helpful in diagnosing brain abscess. However if meningitis is a serious consideration, and the patient has no focal neurological abnormalities and a normal mental status, especially if venous pulsations are present, then emergent LP would be the correct procedure to exclude meningitis. However if the situation is unclear, or if there are neurological abnormalities, then the patient should be first treated with parenteral antibiotics, then scanned, and then tapped if safe based on the imaging results.
Establishing
the correct diagnosis is the major priority for any ED patient with
HA, since rational therapy will more likely follow correct diagnosis.
If meningitis is a real possibility, parenteral antibiotics should be
given as rapidly as possible. Similarly, in the sick patient with brain
abscess (focal or generalized neurological findings), rapid empiric
antibiotics should also be given. However in stable patients without
the above findings, and after discussion with the admitted neurosurgeon,
it is reasonable to withhold antimicrobials. This is because parenteral
antibiotics may decrease the ability to get a proper culture, and it
is this result that will guide as many as 2 months of parenteral antibiosis.
This decision must be individualized. The dosages of the antibiotics for most patients are as follows (all are given IV):
The ED physician should admit all patients with brain abscess, barring extenuating circumstances and assuming that neurosurgical expertise is available at the hospital. If not, the patient should be transferred to a center with such expertise. As well, in some cases, even when there is neurosurgical expertise, transfer is reasonable if it is to a center with stereotactic biopsy capability. These patients are almost always admitted to the neurosurgery or neurology service. Antibiotics and needle drainage may cure some patients, who are treated in the cerebritis or early cavity phase. The needle drainage can be accomplished using stereotactic technique.
Brain abscess is a relatively uncommon, and difficult to diagnose entity that causes HA in the ED. That said, once suspected, modern imaging has made that diagnosis far easier to establish. It is important to remember that normal physical exam, absence of fever and a normal WBC count do not exclude brain abscess. Once established, the ED physician must consult neurosurgery, discuss empiric antibiotics and decide about transferring the patient to a center with the required expertise. If meningitis is a serious concern, antibiotics should be rapidly administered.
Headache and Inability to Solve Quadratic Equations Reference
List
Headache and Inability to Solve Quadratic Equations Outcome of Case The diagnostic procedure was a cranial CT scan, both with and without contrast. The non-contrast scan showed a large area of hypodense vasogenic edema in the left frontal lobe. There was ring-enhancement on the enhanced scan. Brain abscess was diagnosed. This patient was transferred to a facility that had both neurosurgical expertise as well as the ability to perform stereotactic biopsy. This latter procedure was performed on the first hospital day. The blood cultures drawn in the ED were negative but the pus that was obtained at biopsy grew out mixed flora, including aerobic and anaerobic streptococci. HIV antibody testing was negative. The patient
was treated for 6 weeks with high dose parenteral penicillin G and metronidazole.
He never required an open surgical procedure and follow-up CT scans
showed gradual resolution of the abscess. His HA disappeared rapidly
and his ability to solve complex mathematical problems improved to his
baseline. This inability to do higher math was his only physical finding,
not unusual for patients with frontal lobe pathology. An extensive evaluation
of his heart, ears, teeth and sinuses never revealed the source for
the abscess, making this patient among the 20-30% who are termed "cryptogenic"
in terms of etiology.
Annotated Bibliography
Headache and Inability to Solve Quadratic Equations Questions 1. The pathophysiology of bacterial brain abscess includes all but which of the following:
2. The most common symptom in awake patients with brain abscess is:
3. Fever is present in most patients with brain abscess
4. In brain
abscess, an LP would be expected to routinely show all of the following
except:
5. Treatment for brain abscess includes antibiotics and always requires open surgical drainage.
6. The causative
organisms in brain abscess are at least partly a function of the pathophysiology.
Answers
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