MM2-thalamic-type sporadic Creutzfeldt-Jakob disease with widespread neocortical pathology

We report an autopsy case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD) with widespread cerebral neocortical pathology. Initial symptoms were progressive insomnia and mental disturbance. Magnetic resonance imaging revealed no high-signal intensity lesions on diffusion-weighted images and later showed gradually progressive cerebral atrophy. Periodic synchronous discharges and myoclonus were not observed. Upon neuropathologic examination, widespread cerebral neocortical involvement with fine vacuole-type spongiform change was observed. Severe degeneration with almost complete neuronal loss, tissue rarefaction, numerous fat-laden macrophages and hypertrophic astrocytosis of the medial thalamic nucleus was evident. The inferior olivary nucleus showed severe involvement with neuronal loss and hypertrophic astrocytosis. In the cerebellar cortex, moderate depletion of Purkinje neurons was evident, with no spongiform change in the molecular layer and no neuronal loss in the granule cell layer. Immunohistochemistry for prion protein (PrP) revealed widespread synaptic-type deposits with some primitive plaque-type deposits in the cerebral neocortex, basal ganglia and cerebellar cortex. PrP deposition was also observed in the brainstem, particularly the tegmentum, substantia nigra and pontine nucleus, and spinal cord, particularly the posterior horn. In the medial thalamus and inferior olivary nucleus, PrP deposition was sparse. Analysis of the PrP gene showed no mutation but did show methionine homozygosity at polymorphic codon 129. Western blot analysis of protease-resistant PrP indicated the presence of type 2 PrP. We believe that this patient suffered from MM2-thalamic-type sCJD (sporadic fatal insomnia) with widespread cerebral neocortical pathology due to prolonged disease duration. The present case showed different patterns of spongiform degeneration and PrP deposition in the cerebral neocortex than those in previously reported MM2-thalamic-type sCJD cases.