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A patient with Creutzfeldt-Jakob disease presenting with amyotrophy: a case report

Introduction Creutzfeldt-Jakob disease (CJD) is an ultimately fatal, neurodegenerative disease caused by misfolded prion protein aggregation and accumulation. The development of amyotrophic features has been described in CJD, though rarely as an early or prominent feature. Consequently, the significance of amyotrophy in prion disease etiology remains unclear. Case presentation Our patient, a healthy 70-year-old French/Algerian man, presented to our hospital following a work-related fall and was admitted with lower limb skeletal muscle atrophy and fasciculations; the fasciculations progressed to involve the trunk, upper limbs and face. Within days, he developed evidence of a progressive ascending neurological syndrome and subsequent brain involvement with supranuclear palsy of upgaze, catalepsy and death 36 days after symptom onset. Amyotrophy remained the principle feature of his disease. Dementia started to develop within 10 days of the onset of his amyotrophy. Prion disease was confirmed at postmortem. Conclusions Our observations suggest an unusual form of prion disease with prominent early involvement of anterior horn cells, ascending prion propagation in the central nervous system and a grave prognosis.


Introduction
Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia caused by prion protein propagation [1,2]. Amyotrophy is characteristic of amyotrophic lateral sclerosis (ALS), although its presence throughout the clinical course of CJD has been described [3]. However, the significance of lower motor neuron involvement in prion disease etiology is disputed [4,5], and the suggestion of an amyotrophic variant of the disease has been discredited [3,4]. Amyotrophy in CJD has been viewed as a terminal phenomenon in emancipated patients [4]; though Worrall et al. [3] highlight the occasional predominance of amyotrophic features throughout the disease course. Patients with the suspicion of a prion disease and amyotrophy are important to study as they potentially expand the clinical spectrum of the prionopathies.
This article charts the clinical course of marked early amyotrophic features from symptomatic onset until our patient's death. Fasciculations and muscle atrophy remained prominent, with clinical evidence to suggest step-wise, ascending prion propagation from our patient's lower limbs, trunk, upper limbs and finally brain. A diagnosis of sporadic CJD was confirmed at postmortem.

Case presentation
A 70-year-old French/Algerian man presented to our hospital following a work-related fall. He had full functional capacity in all acts of daily living including driving, lived independently and was working until the day of his presentation. An initial physical examination revealed the presence of fasciculations in all muscles of the lower limbs, warranting further investigation and admission. The patient had stable non-insulin-dependent diabetes mellitus.
An initial neurological assessment revealed normal cognition, speech and swallowing. An examination of his central and peripheral nervous systems revealed no diagnostic abnormalities, other than the fasciculations in the lower limbs with mild asymmetrical leg weakness ( Table 1, Day 1). His mini mental state examination result of 25 and clock drawing test measurement of four out of five were considered within normal limits for a French/Algerian man of age 70 where English was not his first language. Furthermore, his Addenbrooke's cognitive assessment and total functional capacity were normal. There were no upper motor neuron signs and the patient could walk without assistance. An initial magnetic resonance imaging (MRI) scan did not show diagnostic abnormalities in the brain or cervical spine. Nerve conduction studies were normal and an electromyography (EMG) test on day 9 showed widespread active and chronic partial denervation in all skeletal muscle sampled: fibrillation and fasciculation potentials were present in all examined muscles and in all four limbs.
A week following presentation, our patient experienced increased difficulty walking with worsening leg weakness (Table 1, Day 7). The fasciculations had ascended and were now clinically evident in the lumbar and thoracic paraspinal muscles and upper limbs.
Electroencephalography (EEG) revealed nonspecific slow wave changes without epileptiform activity. Our patient's symptomatic progression continued and by day 10  A postmortem examination revealed patchy neuronal loss, mild reactive astrogliosis and numerous diffuse neuritic plaques within the brain, with several leptomeningeal and cortical blood vessels positive for beta-amyloid: all compatible with our patient's age, and without neurofibrillary tangles. Spongiform change was widespread in the neocortex. Immunohistological staining for the 12F10 prion antibody revealed patchy synaptic-like positivity in the cerebral cortex, thalamus, cerebellar cortex and brainstem motor neurons. The brain and spinal cord were macroscopically normal. Our mortuary does not permit spinal cord sampling for prion disease and our neuropathology laboratory does not perform prion protein isotyping. Such observations strongly suggested an unusual form of prion disease with prominent early involvement of anterior horn cells and ascending spinal propagation.

Discussion
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][5][6][7], although mostly as a terminal consequence of the disease [4]. 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 [3], making the rapidity of our patient's deterioration and death striking.  • Extensive spongiform change, neuronal loss and astrocytosis in the neocortex, with 12F10 synaptic immunopositivity in cerebral cortex, thalamus, cerebellar cortex and brainstem motor neurons.
ND not described.