A 76-year-old woman presented with a history of quadriparesis from three years ago, initially in the lower extremities and ascended towards the upper extremities (symmetrical and progressive). Neurological examination revealed mild quadriparesis, spasticity, hyperreflexia, bilateral Babinski sign, and fasciculations in the infraspinatus muscle. Magnetic resonance imaging revealed bilateral thalamic lesions, where a broad differential diagnosis was made, which included transmissible spongiform encephalopathies (TSEs). Because of this atypical finding, magnetic resonance imaging could identify it as a variant of Creutzfeldt-Jakob disease (CJD).

Neuropsychological studies revealed fronto-subcortical syndrome characterized by mild cognitive impairment (MCI) with memory loss and abnormalities in visuospatial capacity, and fronto-executive function. The neuropathological study revealed TSEs with predominantly subcortical and motor cortex involvement, which is congruent with CJD. Furthermore, it was associated and congruent with amyotrophic lateral sclerosis (ALS), incipient stage III argyrophilic grain disease per staging of argyrophilic grains 1, and Alzheimer’s disease neuropathologic change, classified as stage A2B1C2 (Braak stage I, Thal phase 3, Consortium to Establish a Registry for Alzheimer’s Disease score moderate) of the National Institute on Aging and Alzheimer’s Association classification system (2012) 2.

The presence of amyotrophy in CJD as a first symptom is very rare 3. The patient’s symptoms initially resembled a clinical presentation of ALS. Moreover, prion transmission originated in the anterior horn cells, ascending to the corticospinal tracts, and eventually to the brain. The presence of MCI clearly attributed to CJD. Although changes in Alzheimer’s disease were evidenced in neuropathology, these were insufficient to describe the cognitive symptoms.