The prion protein disorder CJD is a human transmissible spongiform encephalopathy (TSE) that leads to rapid decay of brain tissue. Human prion diseases are either idiopathic such as sporadic or spontaneous CJD (sCJD), genetic or familial (fCJD), acquired such as iatrogenic CJD (iCJD), or variant CJD (vCJD). The most common form is sCJD, which accounts for about 85% of all known cases. Spontaneous CJD is a rare fatal disorder with rapid progression, an incidence of approximately 1/million/year, and a mortality of >90% within 1 year. The aetiology of sCJD is not known, but the pathogenesis is related to conversion of the normal membrane prion protein PrPc to the pathological form PrPSc. Immunohistochemical demonstration of PrPSc provides a definite diagnosis of CJD at autopsy or by brain biopsy.1
Sporadic CJD chiefly affects people between 50–75 years of age, but can occur as early as adolescence, and as late as the ninth decade of life. The median disease duration in sCJD (6 months) is shorter than in vCJD (14 months). Symptoms of sporadic CJD can appear at 50–70 years of age. It is characterised with rapidly progressive dementia and myoclonus. Personality changes accompany cerebellar and visual symptoms. Ataxia is more pronounced in advanced cases and most patients have myoclonus manifesting as response to auditory and tactile stimuli. In later stages, patients develop akinetic mutism and myoclonus can disappear.
The clinical diagnosis in sCJD is supported by the detection of periodic sharp and slow wave complexes (PSWC) in the EEG, hyperintense basal ganglia on MRI, and 14-3-3 proteins in the cerebrospinal fluid (CSF). Zerr et al
found that 14-3-3 protein is 94% sensitive and 84% specific for the disease.2
The 14-3-3 proteins are evolutionarily conserved proteins present in the cytoplasm of brain neurons at a concentration of about 1% of the total protein content. It has been suggested that 14-3-3 protein as a premortem immunoassay marker may obviate the need for a brain biopsy in the diagnosis of CJD. Although 14-3-3 protein is known to be non-specific, it is included in the World Health Organization criteria for CJD.3
Alzheimer’s disease and Lewy body dementia are the most frequent differential diagnoses in elderly patients, while chronic inflammatory CNS disorders have to be considered in younger patients.
The illness is usually distressingly rapid. Three quarters of people with sCJD die within 6 months of diagnosis, while others die within just a few weeks. Eighty per cent of patients die from infection and cardiac and respiratory failure within the first year.4
At present, there is no proven remedy for prion associated disease. In the UK the CJD Surveillance Unit, based in Edinburgh, can mobilise the substantial package of support which is now available for patients with CJD, and, in the interests of accurate disease surveillance, it is vital that all cases should be reported to the unit.
To our knowledge, this is the first reported case of a newly diagnosed sCJD who presented with florid psychotic features and tonic-clonic seizures, who was diagnosed more than two-and-a-half years ago, and is still alive despite the fact that three quarters of people with sCJD die within 6 months of diagnosis, while others die within just a few weeks.
- Detailed history and investigations can suggest the diagnosis and management in unusual clinical situations.
- This case demonstrates that there are some illnesses that are difficult to be diagnosed, as clinicians cannot be sure about their nature.
- Physicians/psychiatrists should be alerted to consider a diagnosis of CJD, even if the patient has been diagnosed a long time ago.
- For patients presenting with florid psychotic features, physicians/psychiatrist should consider organic causes.
- A low threshold is needed for undertaking a lumbar puncture for patients presenting with florid psychotic and neurological symptoms.