Contributed by Thomas Robertson, FRCPA (1); Anthony E. Tannenberg, FRCPA (2); Jessie Hiu MPath (3); Jon Reimers, FRACP (4)
(1)Department of Histopathology and Cytology, Royal Brisbane Hospital,
(2)Queensland Medical Laboratory,
(3) Queensland Health Pathology Services (John Tonge Center) & Department of Pathology,
Queen Elizabeth Hospital, Kota Kinabalu, Malaysia,
(4) Mater Medical Center, Townsville, Queensland.
The patient was a 53 year-old man who presented with confusion and amnesia and subsequently suffered rapid progressive cognitive decline over the next few weeks associated with myoclonic jerks. His condition did not improve and he expired just over 3 years after presentation. The patient had a past medical history of adult onset generalized epilepsy beginning the third decade of life. Initially the cognitive decline, myoclonic jerks and epilepsy were not thought to be linked and a clinical diagnosis of Creutzfeldt-Jakob disease was made based on the age of onset symptoms and the aggressive nature of the disease.
GROSS AND MICROSCOPIC DESCRIPTION:
Autopsy restricted to the brain was performed. The brain showed moderate global atrophy with hydrocephalus ex-vacuo. There was mild thickening of the basal leptomeninges and an incidental small old contusion to the left temporal lobe. Apart from these changes there was no other abnormality seen macroscopically.
The light microscopy examination of the hematoxylin and eosin stain sections showed neuronal ballooning change, with affected neurones having a finely granular, pale basophilic tinctorial hue (Figure 1A). This change was most evident in the brainstem, in particular the cranial nerve nuclei and reticular formation. The cerebellum exhibited patchy Purkinje cell loss with Bergmann gliosis. The basal ganglia, nucleus basalis of Meynert, and hypothalamus showed neurone loss and gliosis with residual neurons also showing ballooning change. The hippocampus and amygdala showed ballooned neurons but no discernible neurone loss. The thalamus was relatively spared with only rare neurons showing mild accumulation of intracytoplasmic material. The cortex showed variable ballooning change and neuron loss, most evident in laminae V and VI. The insular cortex appeared the most severely affected.
Histochemical stains revealed affected neurones to be Periodic acid-Schiff (PAS) positive after diastase treatment (Figure 1B). The intracytoplasmic material did not show demonstrable autofluorescence.
Ultra-structural examination demonstrated that the ballooned neurons contained excessive and abnormal lipofuscin lysosomal vacuoles containing granular (Figure 2A), rectilinear (Figure 2A), and fingerprint profiles (Figure 2B) in association with dense osmiophilic (presumably lipid) masses.