ABNORMAL PRION ACTIVITY May lead to degenerative disease in the central nervous system. Creutzfeldt–Jakob disease (CJD), which is a common type of human prion disease, exists in genetic, acquired (variant and iatrogenic), and spontaneous (sporadic) forms. Sporadic CJD (sCJD) is characterized by prominent neurological symptoms, periodic epileptiform discharges on electroencephalogram (EEG), a relatively short disease course, onset in old age, and the presence of 14-3-3 protein in the cerebrospinal fluid (CSF). In contrast, variant CJD (vCJD) is characterized by early presentation of comorbid psychiatric symptoms, slow progression, and onset in early life. Comorbid psychiatric symptoms are less common in sCJD. A prospective study reported that 26% of sCJD patients initially exhibit psychiatric symptoms. Another prospective study found that 63% of sCJD patients eventually exhibit comorbid psychiatric symptoms. The present report describes the case of a man who exhibited unusual early psychiatric symptoms and was diagnosed with probable sCJD according to the World Health Organization (WHO) diagnostic criteria for sCJD.
The patient was a 57-year-old retired man without any psychiatric history. In early 2010, he presented with depression, early morning awakening, anhedonia and chronic back pain. He was treated with sertraline at 20 mg/day for 6 months, and a moderate response was noted. Worsening depression was noted, however, in June 2010. He again exhibited anhedonia, anxiety, a propensity to cry, poor appetite and weight loss. One week later, his mood changed and he exhibited irritability and hypertalkativeness. He also presented with psychotic symptoms including visual hallucination, referential delusion, and persecutory delusion. After being initially admitted to the psychiatric ward of a local hospital, he was later transferred to the psychiatric unit at Taichung Veterans General Hospital because of deteriorating memory function and disorganized behavior. Neurological findings were as follows: Glasgow coma scale (GCS) score: E4M6V3 and deep tendon reflexes 2–3+/2–3+. Basic hematology was normal. Results of two EEG were normal. Diffusion-weighted magnetic resonance imaging (DWI-MRI) of the brain showed hyperintensities in the cerebral cortex and bilateral basal ganglia (Fig. 1). Repeat CSF analysis identified an elevated level of 14-3-3 protein, and repeat EEG showed periodic lateralized epileptiform discharges and slow wave complexes. Gene mutations associated with genetic CJD were not found, and methionine homozygotes were detected at codon 129 of the prion protein gene. The final diagnosis was probable sCJD according to the WHO diagnostic criteria for sCJD. The clinical course of the patient is presented in Table 1.
|Phase of disease progression|
|Prodromal||Early phase||Intermediate phase||Late phase|
|Duration||6 months||3–4 weeks||2 weeks||Months|
|Institutional care||Outpatient care||Psychiatric ward||Neurologic ward||Neurologic ward + palliative care|
|Psychiatric symptoms||Depression, anhedonia||Major depressive disorder: a propensity to cry, weight loss, insomnia||Mood disorder with psychotic symptoms: emotional lability, hypertalkativeness, referential delusions||Rapid progressive dementia with psychotic symptoms|
|Neurological symptoms||Negative||Negative|| |
Poor speech ability
|Investigations||−||Brain CT :no apparent abnormal finding/Normal standard biology|| |
Brain MRI: hyperintensity of basal ganglia
Non-specific EEG changes
Periodic EEG complex
Western blot for 14-3-3 protein in CSF
To our knowledge, genetic CJD may mimic other forms of CJD. One large-scale study noted a high incidence of mutations of the prion protein genes, V180I and M232R, among CJD patients in Japan. In the present patient, the possibility of genetic CJD was excluded by checking for the presence of gene mutations. Further, the present patient had widely fluctuating psychiatric symptoms and deteriorating cognition. It is difficult to distinguish CJD from pure psychiatric disorders. Some reports have described the early appearance of psychiatric symptoms in sCJD, including paranoid psychosis, mania, and depression. EEG is the best available auxiliary means of diagnosing sCJD, with a reported sensitivity of around 60%. Recently, MRI findings have proven to be valuable in the clinical diagnosis of sCJD, especially in the early stage of the disease. The sensitivity and specificity of the combined fluid attenuation inversion recovery (FLAIR) and DWI scanning have been reported to be >90%.[10, 11]
This case reminds us that sCJD patients may initially present with long-lasting psychiatric symptoms. Clinicians should pay attention to subtle neurological signs in patients with atypical mood disorder. Utilizing paraclinical investigations including EEG, CSF (for 14-3-3 protein detection), prion gene analysis, and MRI could help clinicians to make more precise and earlier diagnosis of sCJD.