PMC3662898_01
Gross macroscopic findings on neuropathological examination. Selected examples from each case are presented as three vertical panels with lateral views of the unsectioned brain (upper panel), coronal sections through various parts of the cerebrum (middle panel), and axial sections through the brainstem (lower panel). (A) Case 1: There is mild-to-moderate atrophy with ventricular enlargement and cavum septi pellucidi. Thinning of the corpus callosum and mild depigmentation of the substantia nigra is also evident. (B) Case 2: Unsectioned brain, ventricles, and sections of the midbrain and substantia nigra appear within normal limits with no apparent evidence of neurodegeneration. (C) Case 3: Preferential mild-to-moderate atrophy of frontal and temporal lobes with significant enlargement of ventricles seen on coronal sections. A fenestrated septum pellucidum and atrophied amygdala and hippocampus are also seen on this section. The substantia nigra of this patient shows significant loss of pigmentation. (D) Case 4: There is mild frontal and temporal lobe atrophy with enlarged ventricles and cavum septi pellucidi. Axial sections of the brainstem show normal appearing substantia nigra and a metastatic lesion in the pons. (E) Case 5: Atrophic brain is seen with moderately enlarged ventricles and a normally pigmented substantia nigra. (F) Case 6: Minimal atrophy and ventricular enlargement are seen, and there is mild loss in the substantia nigra.
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Neuropathological examination revealed a brain weight of 1400 g with mild atrophy of the frontal and temporal lobes (Figure 1). Pigmentation of the SN appeared within normal limits (Figure 1). His brain was atrophic with a weight of 1300 g after fixation with moderate ventricular enlargement (Figure 1). Ventricles were mildly dilated (Figure 1).
Selected microscopic findings on neuropathological examination. (A) Case 1: High power view of sample of cerebral cortex stained for hyperphosphorylated-tau shows concentration of neurofibrillary tangles predominantly in the superficial layers of the gray matter and in the depths of sulci, which is characteristic of CTE. (B) Case 2: Magnified motor neuron in ventral horn of spinal cord shows a representative intracytoplasmic TDP-43 inclusion. Inset shows a hyalin inclusion. (C) Case 3: Alpha-synuclein staining showing Lewy bodies and neurites which are seen throughout the cortex, substantia nigra, and locus ceruleus. This patient also had features of CTE (not shown). Inset shows higher power view of cytoplasmic Lewy body. (D) Case 4: Immunohistochemisty showing widespread reactivity against tau-positive neurofibrillary and astrocytic tangles in multiple layers. (E) Case 5: Bielschowsky silver stain showing numerous neurofibrillary tombstones in the hippocampus. (F) Case 6: HandE/LFB and alpha-synuclein staining of representative cortical section showing diffuse Lewy bodies and Lewy neurites. Inset shows Lewy body.
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Immunohistochemically, there was widespread tau-positive neurofibrillary and astrocytic tangles in multiple layers (superficial > deep) of the cortex, especially in the depths of sulci (Figure 2). Microscopic examination revealed numerous NFTs in neurons of the deep cortical layers (Figure 2). On microscopic examination, there was diffuse Lewy body disease with Lewy bodies and Lewy neuritis in the cerebral cortex, olfactory bulbs, indusium griseum, SN and limbic system, including the CA2-4 subdivisions of the hippocampus (Figure 2).