This case report provides an insight into the presentation and manifestations of amyotrophic features in CJD from symptom onset to death. The presence of amyotrophy in CJD has been previously documented [4–7], although mostly as a terminal consequence of the disease . To the best of our knowledge, our patient is the first to have experienced amyotrophic features so early in the disease course and to have symptoms suggestive of ascending prion propagation from lower limbs, trunk musculature, upper limbs and brain (Figure 1). Disease duration is typically six months , making the rapidity of our patient’s deterioration and death striking.
Amyotrophy has been described in both familial and sporadic CJD cases [3, 5]. However, quantifying the prevalence of lower motor neuron dysfunction in CJD is problematic in the absence of a rigorous definition . Moreover, the diversity of clinical amyotrophic manifestations reported in CJD has raised doubts over the significance of concurrent upper and lower motor neuron involvement in prion disease.
Worrall et al.  report 13 patients with sporadic CJD who demonstrate clinically relevant lower motor neuron disease with associated electomyographic denervation [3, 4], concluding that amyotrophy is occasionally a significant feature of CJD (readers are referred to that work for detail of those patients). However, the clinical progression and neuropathological findings of only three of these patients convincingly portray the emergence of amyotrophic features with an undoubted CJD diagnosis (Table 2) [4, 7, 8]. Since Worrall et al.’s findings , reports of amyotrophy in CJD have been scant, with the emergence of lower motor neuron features vague upon a questionable diagnosis. Nevertheless, amyotrophy has been reported in six patients with confirmed CJD [4, 5, 7, 8] (Table 2), although only three provide detailed information of their patient’s clinical course [4, 7, 8].
Amyotrophy appeared in the terminal stages of CJD for the majority of these patients and was not an early or sole presenting feature as in our patient (Table 2). For these patients, prion protein propagation appeared to descend the corticospinal tract with rapidity from the brain, to the cervical spine and then trunk musculature; that is, in contrast to the ascending pattern of neurological dysfunction witnessed in our patient. For one patient, however, amyotrophic features were evident at initial presentation and remained prominent throughout the course of his disease ; marked cognitive deficits including memory loss, confabulation and constructional apraxia developed concurrently – distinct from our patient who developed dementia 10 days after the onset of amyotrophy.
Anterior horn cells and spinal ganglia are rarely investigated, but may explain amyotrophy and peripheral denervation in some patients with sporadic CJD . Significant anterior horn cell loss was verified in five patients [4, 8–10], in conjunction with diagnostic spongiform degeneration in the pyramidal tracts. One patient presenting with neurosensory deficits demonstrated decreased motor neuron density in the ventral horns . Due to the restrictions placed upon our mortuary techniques, our patient’s spinal cord could not be microscopically evaluated. Nevertheless, clinical evidence of ascending anterior horn cell involvement was suggestive of upward prion propagation.
Supranuclear palsy of upgaze is sometimes found in other neurodegenerative diseases like progressive supranuclear palsy, but is rarely a feature of sporadic CJD . Moreover, our patient’s development of catalepsy in the later stages of the disease is further evidence of ascending neurodegeneration.
The absence of upper motor neuron signs, the lack of bulbar involvement and the rapid progression negate the possible coexistence of amyotrophic lateral sclerosis (ALS) and CJD. Furthermore, the findings in our patient do not fulfill recognized diagnostic criteria for definite, probable or possible ALS using the El Escorial, Airlie House or Awaji-shima guidelines [12, 13].
Huntington’s disease has been reported as presenting with motor neuron disease, suggesting that anterior horn cells are vulnerable to the effects of neurodegenerative processes of other etiologies including trinucleotide repeat disorder with protein misfolding, impaired deoxyribonucleic acid (DNA) transcription, ribonucleic acid (RNA) processing interference, apoptosis, cytoplasmic element dysfunction and glutamate excitotoxicity .