and specificity. Culture, acid fast stain, and even polymerase chain reaction (PCR)–based
testing for mycobacteria are available but of incomplete sensitivity, and empiric treatment is
necessary in up to half affected patients.
Outcome is heavily dependent on the patient’s level of function at the time treatment is
initiated. If treatment begins while the patient is neurologically normal, outcomes are
excellent. If initiated in comatose individuals, outcomes are predictably quite poor. Although
treatment for TB in general has been well studied, fewer studies have specifically addressed
TB meningitis (6). If multidrug resistant (MDR) TB is unlikely, three-drug regimens with
isoniazid, rifampin, and pyrazinamide are usually given for two months; at the end of
that time the pyrazinamide is usually stopped and the other drugs continued for up to
10 additional months. If MDR TB is likely, ethambutol or streptomycin is typically added for
the first two months. Corticosteroids are often added initially (except in HIV-infected
individuals) and seem to improve outcomes (4). Neurologic sequelae are common.
Spirochetal Infections
Two spirochetal infections commonly invade the nervous system—Borrelia burgdorferi(the
agent of Lyme disease) andTreponema pallidum(syphilis). Both commonly cause meningitis
quite early in infection. In both, the basilar meningitis can be accompanied by cranial
neuropathies. Both may develop parenchymal nervous system involvement later in infection,
although this appears to be far more common in neurosyphilis.
Lyme Disease
B. burgdorferiinfection, transmitted virtually exclusively by bites of hard-shelledIxodesticks,
typically begins with an asymptomatic skin lesion at the site of inoculation, known as
erythema migrans. Prevalent in areas of the Northeast and Upper Midwest United States (7), as
well as much of temperate Europe, this is a multisystem infectious disease that involves the
nervous system in 10% to 15% of untreated patients (8). Meningitis occurs in up to 10% of
patients, who also can develop cranial neuritis and peripheral nerve involvement. Only rarely
is the brain or spinal cord parenchyma directly involved, although many patients with
systemic infection may develop a “toxic metabolic” encephalopathy as a result of the systemic
inflammatory response (9–11).
This encephalopathy well exemplifies the difficulty many nonneurologists have had
differentiating between brain infection and the physiologic effects systemic infection (and the
immune response to it) can exert on the nervous system. Affected patients often describe
cognitive slowing, memory difficulty, and other nonspecific symptoms reflecting the ongoing
presence of a chronic indolent infection—symptoms that typically resolve with successful
treatment. Unfortunately many patients and physicians conclude that these symptoms mean
that the spirochetes have infected the brain and fear that this will lead to inevitable and
progressive neurologic decline. It is now quite clear that most of these patients do not have
CNS infections and that simple oral antimicrobial regimens will cure virtually all of them.
Very rare patients with neuroborreliosis will develop infection within the parenchyma of
the brain or spinal cord—encephalomyelitis. Such individuals, who generally have abnormal
neurologic examinations, abnormal MRI scans, and abnormal spinal fluid, are similarly
responsive to conventional courses of antimicrobials (12).
Diagnosis in general is confirmed with two-tiered antibody testing. An initial screen is
performed using an ELISA; sera judged to be borderline or positive (antibody concentration 2
and 3 standard deviations above the mean, respectively) are then assessed for specificity with a
Western blot (13). The serologic response may take four to eight weeks to be measurable, so in
patients suspected of having very early disease, a follow up ELISA in one to two months is
reasonable. However the rash, erythema migrans, is virtually pathognomonic; in endemic
areas patients with this rash should be treated regardless of serologic results (which can be
negative in up to 50% of these individuals) (14).
In patients without parenchymal involvement (a group that includes those with
meningitis) oral doxycycline 200 mg daily for two to four weeks is generally effective. In
Encephalitis and Its Mimics in Critical Care 157