DIAGNOSTIC EVALUATION A definitive diagnosis of central nervous system toxo- plasmosis requires a compatible clinical syndrome, identi- fication of one or more mass lesions by brain imaging, and detection of the organism in a biopsy specimen. 4 However, the majority of clinicians initially treat a seropositive pa- tient with compatible symptoms, signs, and imaging for presumptive TE, reserving a biopsy in those who do not improve (clinically or radiographically) after two weeks of directed therapy. The vast majority of patients with toxo- plasma encephalitis are seropositive for anti-toxoplasma IgG antibodies. 21 Anti-toxoplasma IgM antibodies are usually absent; quantitative IgG antibody titers are not helpful. The absence of antibodies to toxoplasmamakes the diagnosis less likely but does not exclude it. 4 Magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for identifying cerebral toxoplasmosis, which usually presents as multiple, ring-enhancing brain lesions often associated with edema. 22,23 Thallium single photon emission computed tomography (SPECT) and positron emission tomography (PET) can be useful in distinguishing toxoplasmosis or other infections fromCNS lymphoma. 24,25 Lymphoma has greater thalliumuptake on SPECT and greater glucose andmethio- nine metabolism on PET than neurotoxoplasmosis or other infections. 26,27 Cerebrospinal fluid (CSF) may demonstrate a mild mononuclear pleocytosis and elevated protein level. Tachyzoites can occasionally be seen on cytocentrifuged cerebrospinal fluid samples stained with Giemsa. Detection of T. gondii by PCR has demonstrated high specificity (96% to 100%) but variable sensitivity (50% to 98%). 28,29 Thus, a positive PCR result establishes the diagnosis, but a negative test does not rule it out. PROPHYLAXIS AND TREATMENT Treatment usually consists of a combination of medica- tions for six weeks. The regimen of choice is pyrimethamine and sulfadiazine. 4,30-32 Patients who are intolerant to sulfa- diazine can take clindamycin. 4,33 Alternative regimens for those who do not tolerate more standard regimens include trimethoprim-sulfamethoxazole, or pyrimethamine plus azithromycin, or pyrimethamine plus atovaquone, or sulfa- diazine plus atovaquone, or atovaquone. 4,34,35 All pyrimeth- amine-containing regimens should also include leucovorin (folinic acid) to prevent drug-induced hematologic toxicity. Adjunctive corticosteroids should be used for patients with radiographic evidence of midline shift, signs of critically el- evated intracranial pressure, or clinical deterioration within the first 48 hours of therapy. 36 Anticonvulsants should be ad- ministered to patients with a history of seizures but should not be given routinely for prophylaxis to all patients with the presumed diagnosis of CNS toxoplasmosis. 4 Immune reconstitution inflammatory syndrome (IRIS) can lead to a paradoxical worsening of symptoms with development of worsening edema surrounding brain lesions as CD4 cell counts rapidly improve. 37-39 Management of IRIS includes
AIDS, there is no higher incidence of toxoplasmosis in cat owners compared to non-cat owners. 6 Patients who are HIV-infected with <100 CD4 cells/ mm 3 , and are toxoplasma seropositive have an approxi- mately 30% probability of developing reactivated toxoplas- mosis in absence of prophylaxis. 7, 8 Themechanismbywhich HIV induces susceptibility to toxoplasmosis appears to be multifactorial, including depletion of CD4 T cells; impaired production of IL-2, IL-12, IFN-gamma; and impaired cyto- toxic T-lymphocytic activity. 9 The introduction of anti-toxoplasma prophylaxis and potent antiretroviral therapy (ART) has altered the occur- rence of toxoplasmic encephalitis. 10 In the Multicenter AIDS Cohort Study (MACS), the incidence of CNS toxoplasmosis decreased from 5.4 per 1,000 people in years 1990 to 1992 to 3.8 per 1,000 people in years 1993 to 1995, and 2.2 per 1,000 people in years 1996 to 1998. 11 It is much harder to determine the incidence of extra- cerebral toxoplasmosis. Most of the available data is from before the introduction of ART and from France, where the seroprevalence to T. gondii is high. The most prominent risk factor for the development of extracerebral toxoplasmosis is advanced immunosuppression (mean CD4 cell counts of 57 and 58 cells/mm 3 ). 12,13 Concurrent CNS disease was present in 41% of patients in the report of 199 extracerebral cases. 13 CLINICAL PRESENTATION Eighty to ninety percent of acute T. gondii infections in immunocompetent hosts are asymptomatic. When symptomatic infection does occur, the most common manifestation is bilateral, symmetrical, non-tender cervical lymphadenopathy. 14,15 Twenty to thirty percent of symp- tomatic patients will have generalized lymphadenopathy. Constitutional symptoms, such as fever, chills, and sweats may be present but are typicallymild. Headaches, myalgias, pharyngitis, diffuse non-pruritic maculopapular rash, or hepatosplenomegaly may also occur. Most immunocompe- tent patients have a benign, self-limited course lasting from weeks to months, but rarely longer than a year. 16 T. gondii usually reactivates in patients with AIDS, most commonly doing so in the CNS leading to cerebral abscesses. Patients with cerebral toxoplasmosis typically present with headache, confusion, and fever. 6 This disease is an impor- tant cause of focal brain lesions in HIV-infected patients. 8,17 Characteristically, toxoplasma-associated encephalitis has a subacute onset with focal neurologic abnormalities fre- quently accompanied by headache, altered mental status, and fever. 18,19 The most common focal neurologic signs are motor weakness and speech disturbances. Patients can also present with seizures, cranial nerve abnormalities, visual field defects, sensory disturbances, cerebellar dysfunction, meningismus, movement disorders, and neuropsychiatric manifestations. 18,19 Toxoplasmosis rarely presents as a rap- idly fatal form of diffuse encephalitis. 20
J La State Med Soc VOL 166 January/February 2014 43
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