Symptoms of prion disease can vary widely and often mimic other illnesses.
Sporadic CJD presents itself in a variety of ways, though typically looks homogeneous towards the end of the disease duration1,2. Clinical presentation can include a "classic CJD" phenotype, demonstrating cognitive impairment and cerebellar impairment such as gait ataxia or incoordination (MM1 & MV1). However, most cases of CJD do not present with a clinical syndrome that is immediately identifiable as sCJD. Many cases will present with cognitive impairment and may initially be misdiagnosed as a different type of dementia (e.g., Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies)(MV2).
Other cases may present with isolated visual symptoms (i.e., Heidenhain variant, MM1) or pure gait ataxia for a period of time before other symptoms emerge (i.e., Oppenheimer-Brownell variant, VV2). Nevertheless, some cases may present with a non-specific psychiatric syndrome, as a mood disorder or anxiety. It is not unusual for sCJD to be misdiagnosed as other illness because of symptoms that overlap with more common conditions3,4. Oftentimes the illness has to progress and include more common symptoms, such as myoclonus, for clinicians to appropriately arrive at a clinical suspicion of the disease.
The average duration of sCJD is 4-6 months, from illness onset until the patient passes. The majority of patients with sCJD succumb to their illness within a year, but some cases can survive a year or two. However, because of the difficulty in diagnosing sCJD, it is not uncommon for there to be a very short time period between diagnosis and death (e.g., one month). sCJD is typically a disease of mid-to-late life, with an average age of onset in the mid-60's, but with cases as young as 14 and as old as 101.
Variably Protease-Sensitive Prionopathy (VPSPr) is a rare sporadic form of prion disease characterized by speech difficulties and psychiatric signs, followed by cognitive impairment and progressive motor impairment6. Many of these cases have a longer duration than sCJD and are initially misdiagnosed as a non-Alzheimer's type of dementia (e.g., dementia with Lewy bodies, frontotemporal dementia).
1. Appleby B. S., Appleby K. K., Crain B. J., Onyike C. U., Wallin M. T., Rabins P. V. "Characteristics of established and proposed sporadic Creutzfeldt-Jakob disease variants"; Arch Neurol 2009; 66:208–15.
2. Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, et al. "Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects". Annals of Neurology 1999; 46:224–33.
3. Chitravas N, Jung RS, Kofskey DM, Blevins JE, Gambetti P, Leigh RJ, et al. Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease. Annals of Neurology 2011; 70:437–44.
4. Appleby BS, Rincon-Beardsley TD, Appleby KK, Crain BJ, Wallin MT. "Initial diagnoses of patients ultimately diagnosed with prion disease". Journal of Alzheimer’s Disease: JAD 2014; 42:833–9.
5. Cracco L, Appleby BS, Gambetti P. "Fatal familial insomnia and sporadic fatal insomnia". Handb Clin Neurol 2018; 153:271–99.
6. Notari S, Appleby BS, Gambetti P. "Variably protease-sensitive prionopathy". Handb Clin Neurol 2018; 153:175–90.