Prion disease has long had an association with various neuromuscular diseases, but the pathogenic link is not understood.  Specifically, cases of amyotrophy as a feature of prion disease have been reported in case reports and case series.  We present a case of slowly progressing amyotrophy with subsequent cognitive decline which ultimately led to a neuropathologic diagnosis of Gerstmann-Sträussler-Scheinker disease (GSSD). 

Among the prion diseases, GSSD is one of the more commonly inherited forms of prion disease, often accompanied by symptoms of dysesthesias, ataxia, gait instability, and hyporeflexia. 

Prion diseases in general have been well established to be associated with disorders of the neuromuscular system.  These include polyradiculoneuritis, motor neuron disease, disorders of the posterior horn cells, and peripheral neuropathies. 

Our patient was a 57-year-old man with no significant past medical history who presented with a 2 year history of progressive bilateral thigh pain and atrophy, weakness, imbalance, and later developed cognitive difficulties.    His physical examination demonstrated muscle atrophy, weakness, and fasciculations.  His initial brain MRI was normal but a repeat showed diffuse cortical ribboning pattern on diffusion weighted sequences.  NCS/EMG demonstrated diffuse positive sharp waves and fibrillation potentials in the upper and lower extremities, as well as in the thoracic paraspinal muscles.  Cerebrospinal fluid analysis demonstrated positive/elevated protein 14-3-3, T-tau protein, and RT-QuIC.  GSSD was confirmed on genetic sequencing of brain tissue at autopsy, with a P102L-129M mutation in the PRNP gene.

Ultimately, this unique case helps highlight several learning points about these rare diagnoses, including (a) the wide phenotypic range of presentations of prion disease, (b) the importance of neuropathologic examination of spinal cords in addition to brain at autopsy, and (c) the importance of brain imaging and CSF analysis in patients with amyotrophy who develop cognitive symptoms.