Contributed by Giorgio Giaccone1, Francesco Carella1, Carlo Parravicini2, Erika Longhi2, Luisa Chiapparini1, Mario Savoiardo1,
Nicola Montano2,3, Michela Morbin1, Alberto Albanese1, Fabrizio Tagliavini1
1IRCCS Foundation Carlo Besta Neurological Institute, 2Luigi Sacco Hospital, and 3Department of Biomedical and Clinical Sciences, University of Milano, Italy
A 52 year old man with an unremarkable clinical history started to complain of daily somnolence, unusual irritability and some memory lapses. A few months later, he had fever and developed confusion with myoclonic jerks of the left limbs. Upon admission a diagnosis of encephalitis was made. MRI FLAIR images (Figure 1 A, B) showed cortical and sub-cortical abnormal signal intensity in parasagittal posterior frontal and anterior parietal regions, compatible with ischemic damage in watershed areas. On coronal T1-weighted image (insert in Figure 1A) cortex was hyperintense for petechial hemorrhage. Multivoxel Proton Magnetic Resonance Spectroscopy (1 H-MRS) demonstrated lactic acid in the lesions (Figure 1C, arrows). The CSF showed 10 white cells / ml with normal protein and glucose. He was treated with antibiotics, acyclovir, steroids and immunoglobulins and improved so that he was discharged to a rehabilitation facility. The patient could play chess and walk around with the help of a walking frame.
Two months later he again had fever with confusion and inappropriate mood. His myoclonic jerks and weakness was now bilateral. He had decreased alertness and was not able to walk or stand. MRI showed additional lesions in other cerebral regions. Axial FLAIR (Figure 1D), axial DWI (Figure 1E), and sagittal T2-weighted images (Figure 1F) demonstrated acute ischemic stroke in the right temporo-parietal area and in right parietal region at the vertex (insert in Figure 1D). DWI (b 1000 value, Figure 1E) showed a marked hyperintensity due to cytotoxic edema. A small ischemic area was present in the right pulvinar (arrowheads in Figure 1D and F). A total body CT scan showed liver cirrhosis with left pleural effusion. The patient was treated again with antibiotics, acyclovir and antiepileptics without any improvement and a flaccid tetra paresis with muscular atrophy and areflexia developed in few weeks.
The patient was then admitted to our institution with indication for brain biopsy. He was alert, in bad general condition and with fecal incontinence. He responded with vocalization and grimacing to painful stimuli. Hypotonic tetraplegia, diffuse muscle atrophy and areflexia were present with hypotonia more evident in the left limbs. An EMG study provided evidence of a severe axonal sensory-motor polyneuropathy. An EEG showed low voltage activity unresponsive to stimuli as in the alpha-coma condition. Brain MRI demonstrated large gliotic areas and cortex atrophy in the frontal and parietal regions and in the right temporo-parietal area as the result of ischemic strokes, and did not show additional lesions.
An open biopsy of posterior right temporal lobe was performed and showed severe neuronal loss, neuropil vacuolization (Figure 2A) striking gliosis with numerous reactive astrocytes by GFAP (Figure 2B), marked microglial activation. Mild lymphomonocytic perivascular infiltrates were present in the cerebral cortex, subcortical white matter and leptomeninges (Figure 2C, IHC for CD45; 2D IHC for CD68). Myelin showed pallor but no areas of demyelination. Some macrophages harboring Periodic acid-Schiff (PAS)-positive, diastase-resistant material in the cytoplasm were observed in the thickened leptomeninges (Figure 2E) as well as in the neuropil (Figure 2F). What is your diagnosis?