Autopsy case of V180I genetic Creutzfeldt‐Jakob disease presenting with early disease pathology

Abstract

The patient was a Japanese woman who experienced a decrease in activity and gait disturbance as the initial symptoms at the age of 86, followed by disorientation and memory dysfunction. Magnetic resonance imaging showed extensive cortical regions with hyperintensity in diffusion-weighted images, and these regions showed swelling in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The medial occipital cortex and striatum showed no apparent hyperintensity on diffusion-weighted imaging (DWI). Mild myoclonus was detected, and the patient died 10 months after the onset of symptoms; she did not enter the akinetic mutism state. The patient's brain weighed 1050 g, and neuropathological examination showed extensive characteristic various-sized and non-confluent (VaSNoC) vacuoles in the cerebral cortex. These vacuoles were observable macroscopically by loupe on images of hematoxylin and eosin-stained tissue. Gliosis, hypertrophic astrocytosis, and neuron loss were generally mild in character. Prion protein (PrP) immunostaining showed very mild diffuse-synaptic-type PrP deposition in the cerebral gray matter. These clinicopathological findings led us to several conclusions relative to the early disease pathology of V180I genetic Creutzfeldt-Jakob disease: (i) spongiform change was not found in the medial occipital cortex, which corresponds to the results of DWI; (ii) VaSNoC-type spongiform changes, extensively recognized in the cerebral cortex, corresponded to the DWI findings showing continued hyperintensity with higher brightness, and T2-weighted and FLAIR images findings showing a swelling; and (iii) spongiform changes first appear in the deeper layer and subsequently in the superficial layer in the cerebral cortex.

A case of V180I genetic Creutzfeldt-Jakob disease presenting with conspicuous facial mimicry

“…According to previous autopsy case reports of V180I gCJD, the neurons of the cerebral neocortex in such cases show a tendency toward preservation despite the extensive severe spongiform changes and long disease duration [1,6,7,9,10]. Furthermore, the precentral gyrus and in particular the medial portion of the occipital lobe tend to be pathologically preserved in patients with V180I gCJD [1,9,10]. We believe that these pathological observations appear to support our hypothesis.…”

“…Based on the finding of facial mimicry in the present case, we speculate that the function of both visual recognition, including from the optic nerve to the primary visual cortex in the occipital cortex, and facial movement, including the facial nerve nucleus and primary motor cortex in the precentral gyrus, were preserved, at least during the period that the symptom was observed. According to previous autopsy case reports of V180I gCJD, the neurons of the cerebral neocortex in such cases show a tendency toward preservation despite the extensive severe spongiform changes and long disease duration [1,6,7,9,10]. Furthermore, the precentral gyrus and in particular the medial portion of the occipital lobe tend to be pathologically preserved in patients with V180I gCJD [1,9,10].…”

“…CJD with point mutation of valine to isoleucine at codon 180 of the PrP gene (V180I gCJD) is the most frequent gCJD form in Japan [5], whereas this variant is extremely rare in Europe and North America [3]. According to several previous reports, the clinical features of V180I gCJD are relatively uniform but significantly differ from those of typical sporadic CJD as follows [1,[6][7][8][9][10]: (1) onset at an older age, (2) prolonged disease duration with a slower course of progression, (3) early stages of the disease characterized by cerebral cortical symptoms, such as aphasia, apraxia, and dementia, but without visual or cerebellar involvement; (4) a lower positive rate of brain-specific proteins such as neuron-specific enolase, total tau protein, and 14-3-3 protein in the cerebrospinal fluid (CSF); (5) absence of PSWCs on EEG throughout the disease course, (6) less prominent myoclonus with a later onset, and (7) rarely present family history of the disease. Furthermore, conspicuous pathological laughing and startle reaction observed in the early disease stage are also frequently present in V180I gCJD [8][9][10].…”

Clinicopathological findings of a long-term survivor of V180I genetic Creutzfeldt-Jakob disease

“…A previous report indicated that the survival period of tube-fed patients with sCJD is longer than that of patients who were not tube fed [20]. To understand the timing of starting tube-fed or total parenteral nutrition (TPN), we reviewed 14 patients with autopsy-confirmed V180I gCJD including the current patient (Table 1) [8,[21][22][23][24][25][26][27][28][29][30][31][32][33]. Combined V180I and M232R gCJD patients were excluded from our review.…”

Recent advances in the histo‐molecular pathology of human prion disease

“…Similarly, several neuropathological features that are associated with the V180I‐129M/PrP Sc type 2 combination, including the florid spongiform change lacking confluent vacuoles, as well as the faint synaptic type pattern of PrP immunostaining, do not fully match those of the sCJDMM2 subtypes .…”