Brain Pathology Case of the Month - July 2013


Toxoplasmosis of the hypothalamus


The immunohistochemical study revealed numerous tachyzoites in the necrosis area and small cysts containing bradyzoites around the necrosis area. This method allows distinguish Toxoplasma cysts from cysts seen in other infections such as Trypanosoma cruzi and Leishmania donovani (4). Toxoplasmosis is the most common opportunistic infection involving the central nervous system in patients with the acquired immunodeficiency syndrome (AIDS), representing 7-39% of the focal brain lesions found in autopsy (3). The number of cases has markedly decreased after the introduction of HAART (6). The variable neurologic manifestations of cerebral toxoplasmosis associated with AIDS sometimes make it difficult to obtain a definite diagnosis during life. The most common clinical presentation of cerebral toxoplasmosis is the effect of a solitary or multiple mass lesion, usually located in the basal ganglia or thalamus, or lobar at the gray-white matter junction (3). When, as in our patient, the infection is located in non-habitual sites, resulting in atypical clinical manifestations, and does not produce a space-occupying brain lesion, it becomes much more difficult to achieve the correct diagnosis. There was unequivocal histological evidence of active cerebral toxoplasmosis at autopsy, despite the lack of toxoplasma specific IgM in the serum. To our knowledge, this is the first report of central diabetes insipidus in a patient with AIDS due to solitary hypothalamic toxoplasmosis confirmed at autopsy. Our patient presented with clinical and laboratory evidence of probable central diabetes insipidus, which was confirmed by the good clinical response to the treatment with desmopressin. Although endocrine evaluation to determine the presence of secondary adrenal insufficiency was not made, the finding of refractory hypotension and episodic hypoglycemia suggests a hypothalamo-pituitary axis disorder (1). Furthermore, chronic and recurrent hyperthermia is described in cases of lesions in the medial pre-optic region located in the periventricular zone bordering the lateral wall of the third ventricle, known as the central thermostat (10). Diffuse, bilateral and almost symmetrical hypothalamic involvement by the necrotic-inflammatory process may explain all clinical manifestations of our patient: diabetes insipidus, recurrent hyperthermia, and possible secondary adrenal insufficiency (5). The presence of lipid-laden macrophages, microvascular proliferation, fibrosis and gliosis surrounding the necrosis indicates a sub-acute presentation lesion, compatible with the initial clinical manifestations lasting three months. The relative small size of the hypothalamic lesion and limited extension of the inflammatory infiltrate in the adjacent leptomeninges also may explain the absence of focal neurologic deficits and signs of meningeal irritation. Hypothalamo-pituitary dysfunction caused by cerebral toxoplasmosis has rarely been reported in patients with AIDS. To date, there are reports of only three patients with AIDS and cerebral toxoplasmosis who had clinical evidence of hypothalamo-pituitary dysfunction (2, 7, 9). Two of these patients presented central diabetes insipidus, one of them isolatedly (9) and the other one in association with panhypopituitarism (2). A good clinical response was obtained after empirical treatment for cerebral toxoplasmosis. The third patient presented diabetes insipidus associated with corticotropic insufficiency (7). A solitary hypothalamopituitary lesion was demonstrated on MR imaging. Testing of cerebrospinal fluid revealed a PCR positive for Toxoplasma gondii and there was almost complete regression of the lesion after antiparasitic treatment was initiated. The patient reported by Milligan et al. (8) presented clinical and laboratory evidence of anterior panhypopituitarism. The diagnosis of toxoplasmosis was established by brain biopsy and at autopsy. The anterior pituitary was necrotic, with a sparse lymphocytic infiltrate. Several brain regions were involved, but not the hypothalamus. In conclusion, this is the first reported case of toxoplasmosis presenting with central diabetes insipidus, recurrent hyperthermia, and possible secondary adrenal insufficiency, all produced by solitary involvement of the hypothalamus diagnosed at autopsy in a patient with AIDS. Although central diabetes insipidus and other signs of hypothalamic involvement appear to be a rare presentation of cerebral toxoplasmosis in patients with AIDS, it should be considered in cases of central diabetes insipidus of unclear cause, even when only a solitary lesion is apparent.


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Contributed by José Eymard Homem Pittella, MD, DSci, Bruno Lopes dos Santos, MD, Gustavo Novelino Simão, MD, MSci, DSci, Fernando Crivelenti Vilar, MD, Rodrigo de Carvalho SantanaMD, DSci

International Society of Neuropathology