VII. Neuropathology of T. gondii
The neuropathology of schizophrenia is subtle, with mild atrophy and dilated ventricles. The brain regions of greatest interest have been the prefrontal cortex, hippocampus, and association cortex, which includes the superior temporal gyrus and inferior parietal lobule; other areas, such as the cingulate, basal ganglia, thalamus, and cerebellum, are also thought to be involved. Abnormalities have been described in both neurons and glia.
The neuropathology of congenital toxoplasmosis has been well described. It consists of periaqueductal and periventricular vasculitis with necrosis. Obstruction of the aqueduct may produce hydrocephalis and the necrotic tissue may calcify (Frenkel JK, Pathology and pathogenesis of congenital toxoplasmosis, Bull NY Acad Med 1974;50;182–191).
The neuropathology of T. gondii infection acquired after birth has been less completely described except for cases of immunosuppression, such as AIDS. In one of the few cases reported, a 6-year-old boy died from acute toxoplasma encephalitis and was autopsied one hour after death. According to the report, “there was no gross pathologic change . . . [and] the paucity of microscopic abnormalities was equally surprising.” The author concluded: “It is also remarkable how the observations in this case differ from the extensive, gross and microscopic changes which have been observed in the one proved case of ‘congenital’ encephalitis due to toxoplasma (Sabin AB, Toxoplasmic encephalitis in children, JAMA 1941;116:801–807). Other case reports have also noted the paucity of CNS findings in adult toxoplasmosis; however, one study reported widespread pathological findings in other organs, including the liver and spleen (Callahan WP, Russell WO, Smith MG, Human toxoplasmosis: a clinicopathologic study with presentation of five cases and review of the literature, Medicine 1946;25:343–397).
T. gondii is known to be highly neurotropic and to infect both neurons and astrocytes (Halonen SK, Lyman WD, Chiu FC, Growth and development of Toxoplasma gondii in human neurons and astrocytes, J Neuropath Exp Neurol 1996;55:1150–1156; Cruzet C, Robert F, Roisin MP et al., Neurons in primary culture are less efficiently infected by Toxoplasma gondii than glial cells, Parasitol Res 1998;84:25–30). In non-immunosuppressed individuals who are diagnosed with acute toxoplasmic encephalitis, the CSF shows moderately elevated protein, normal glucose levels, and T. gondii “is rarely isolated from the CSF.” Necrosis and an intense inflammatory reaction are seen on autopsy (Post MJD, Chan JC, Hensley GT, Toxoplasma encephalitis in Haitian adults with acquired immunodeficiency syndrome: a clinical-pathologic-CT correlation, Am J Roentgenol 1983;140:861–868). In immunosuppressed individuals, T. gondii may cause an acute necrotizing encephalitis that is most severe in the frontal and parietal lobes, basal ganglia, and thalamus (Shankar SK, Mahadevan A, Satishchandra P et al., Neuropathology of HIV/AIDS with an overview of the Indian scene, Indian J Med Res 2005;121:468–488; Dellacasa-Lindberg I, Hitziger N, Barragan A, Localized recrudescence of Toxoplasma infections in the central nervous system of immunocompromised mice assessed by in vivo bioluminescence imaging, Microbes Infect 2007;9:1291–1298).
Less information is available on the neuropathology of individuals chronically infected with T. gondii with bradyzoites. A study of 46 postmortem cases of AIDS patients with T. gondii infection reported “one case with intact tissue cysts in the parietal white matter as the only histopathologically identifiable lesion” (Strittmatter C, Lang W, Wiestler OD et al., The changing pattern of human immunodeficiency virus-associated cerebral toxoplasmosis: a study of 46 postmortem cases, Acta Neuropathol 1992;83:475–481).
- Neuropath studies of T. gondii in schizophrenia
One study has been carried out. Conejero-Goldberg studied the orbital frontal cortex of postmortem specimens from 14 individuals with schizophrenia, 11 with other psychiatric diagnoses, and 26 normal controls. The primers “were designed to amplify a conserved region in the parasitic genome and a fragment of the hsp/Bag1gene (a bradyzoite-expressed gene)” using a nested polymerase chain reaction. All specimens were negative (Conejero-Goldberg C, Torrey EF, Yolken RH, Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients, Schizophr Res 2003;60:65–69).