Brain Pathology Case of the Month - July 2013

Contributed by José Eymard Homem Pittella, MD, DSci1, Bruno Lopes dos Santos, MD2, Gustavo Novelino Simão, MD, MSci, DSci3, Fernando Crivelenti Vilar, MD4, Rodrigo de Carvalho SantanaMD, DSci4

1Department of Pathology, 2Movement Disorders and Behavioral Neurology Unit, Department of Neurosciences and Behavioral Sciences, 3Radiology Division, 4Division of Infectious Diseases, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.


CLINICAL HISTORY

A 39-year-old man was admitted with recurrent fever, dizziness and headache of three months' duration. He related appetite loss and weight loss of 10 kg in the last three months. He had been diagnosed with HIV infection nine years before, but had never made use of highly active antiretroviral therapy (HAART). On physical examination, he was afebrile, confused, emaciated and presented oral candidiasis. There were no focal neurologic deficits or signs of meningeal irritation. Laboratory studies revealed a CD4 cell count of 101 cells/mm3, a viral load of 500,000 copies/ml, and serum sodium concentration of 145 mmol/liter. A blood test revealed increased levels of IgG for Toxoplasma gondii, with a negative IgM. A cerebrospinal fluid test revealed mild lymphocytic pleocytosis, elevated protein levels, and hypoglycorrhachia. No bacteria and fungi were identified with Gram, Ziehl-Neelsen, and India ink staining. At day 4, the serum sodium concentration increased to 155 mmol/liter. A computerized tomography of the head showed a slight edema and contrast enhancement in the hypothalamic area (Figure 1). At day 5, the patient complained of intense thirst and presented polyuria, hypotension, and elevated levels of serum urea and creatinine. The serum sodium concentration remained high (164 mmol/liter), even after hypotonic fluid infusion. Urine analysis revealed low osmolality, low sodium concentration, and low density. A diagnosis of probable central diabetes insipidus and acute renal failure due to dehydration was established and treatment with desmopressin by nasal spray was initiated. At day 7, the patient developed pneumonia and his general condition worsened. He was transferred to the Intensive Treatment Unit and maintained under the same antibiotic regime. He died two days later (nine days after admission). A post-mortem brain MRI showed symmetric hyperintensities at the floor of the third ventricle in the hypothalamus on axial T2-weighted images (Figure 2).

NEUROPATHOLOGY

The major autopsy findings consisted of bilateral bronchopneumonia complicated by septic shock. The brain was examined four weeks after fixation in buffered formalin. There was a whitish thickening of the leptomeninges at the brain basis, particularly between the optical chiasm and the superior part of the pons. Coronal sections showed no changes (brain weight: 1,375g). On histological examination, a central area of coagulative necrosis extending to blood vessels, with variable fibrinous exudate and partially permeated by polymorphonuclear neutrophils, was seen bilaterally and almost symmetrically throughout the length of the hypothalamus, i.e., at the supraoptic, infundibular (Figure 3), and mamillary (Figure 4) levels. Surrounding the necrosis (Figure 5) were lipid-laden macrophages, lymphocytes, plasma cells, newly formed vessels, fibrosis, and gliosis (Figures 6 and 7). The inflammatory infiltrate extended to the overlying leptomeninges. Research for bacteria, mycobacteria and fungi was negative in histological sections stained by specific staining techniques (Gram, Ziehl-Neelsen and Methenamine Silver). A diagnostic immunohistochemical study was done (Figure 8). There was no evidence of infection in other brain regions. The pituitary gland showed no changes.

FINAL DIAGNOSIS


International Society of Neuropathology