Case 724 -- Neurological deterioration despite aggressive treatment in a man with AIDS

Contributed by González-Duarte, A*, Saniger, M*, Arispe-Angulo K**, Gamboa-Dominguez A**, García-Ramos, G*.
*Department of Neurology and **Pathology of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.


A 47-year old Hispanic male with end-stage AIDS was admitted to the hospital with pneumonia, altered mental status and right-sided weakness. His previous medical history was obscure. He had never received antiretroviral treatment. Upon his arrival he was cachectic, tachycardic and lethargic. His neurologic exam showed left facial palsy, right hemiparesis, hyperreflexia, and a positive right Babinski sign. He had no signs of meningeal irritation. On admission his white blood cell count was 8400/mm3 (98% neutrophils), and his CD4+ cell count was 8 cells/mm3. The serum cryptococcal antigen was negative. IgG and IgM toxoplasma antibodies were positive. A MRI was ordered which was suggestive of neurotoxoplasmosis. He was started on piperacillin-tazobactam, clarithromycin and trimethoprim / sulfamethoxazole for pneumonia, valgancyclovir for skin biopsy proven CMV infection, fluconazol for oral candidiasis and pyrimethamine and clindamycin for toxoplasmosis. Although he continued disoriented and sleepy, he was stable for a few days. On the 18th hospital day he developed severe respiratory distress. He became stuporous and presented right midriasis and ptosis, impaired adduction of the right eye, and generalized seizures. He required immediate ventilatory support and high doses of vasoactive amines. Intravenous amphothericin B infusion was started in order to broaden the antimicrobial coverage, but the patient died five days later.


Neutrophil cell counts during his stay were always within the normal range. The initial CSF analysis showed 20 cells/mm3 (95% of PMN), glucose of 51 mg/dL (serum glucose of 90 mg/dL), proteins of 44 mg/dL, and negative PCR for VHS, VHZ, CMV and M. tuberculosis. The Gram stain was negative for organisms, and subsequent cultures for bacteria and fungi were without growth. India Ink stain and cryptococcal antigen in the CSF were negative. A second CSF analysis showed no signs of inflammation, with cero cells/mm3, proteins of 55 mg/dL and glucose of 69 mg/dL (serum glucose of 90 mg/dL). All blood and CSF cultures continued to be negative.

An axial T2 FLAIR and T1 MRI with gadolinium of the brain performed before initiating anti-toxoplasmosis treatment showed multiple non-enhancing hyperintense lesions (Figures 1, 2). A subsequent MRI showed marked improvement, with evident reduction in size of the previous lesions (Figures 3, 4, 5). A third MRI performed after the neurological deterioration showed bilateral well-demarcated T2 FLAIR hyperintense lesions without contrast enhancement, and high signal-intensity lesions in the diffusion-weighted images, suggestive of early ischemic areas (Figures 6, 7, 8).


On post-mortem inspection, the fresh brain weighted 1390 grams. On gross assessment, multiple ischemic and hemorrhagic mass lesions in the brainstem, basal nuclei, internal capsule, corpus callosum, frontal, parietal and occipital hemispheres were seen (Figures 9, 10, 11, 12). The left occipital lobe was completely necrotic (Figure 12). There was no basal meningitis. Microscopically, hematoxylin and eosin (13, 14) and Grocott (Figure 15) stained preparations on multiple sites showed numerous septated, 45 angle dichotomous branching hyphae. There was widespread infiltration of the parenchyma (Figure 13) and blood vessel walls (Figure 14). Penetration into the vessel walls was associated with a diffuse inflammatory response, multiple hemorrhagic infarcts and necrosis. A recent right parietal subarachnoid hemorrhage with acute inflammation in the surrounding parenchyma was also present (Figure 16). Two small subacute infarcts were seen in the frontal lobes.


Case IndexCME Case StudiesFeedbackHome