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BMJ Case Rep. 2010; 2010: bcr12.2009.2576.
Published online May 13, 2010. doi:  10.1136/bcr.12.2009.2576
PMCID: PMC3047567
Rare disease
An unusual case of sporadic Creutzfeldt-Jakob disease (CJD)
Qaiser Javed,1 Faouzi Alam,2 Sowmya Krishna,3 and Geetha Jaganathan2
1University Hospital Aintree, Psychiatry, Ferndale Unit, Lower Lane, Liverpool L9 7AL, UK
2St Catherines Hospital, Psychiatry, Stein Centre, Church Road, Birkenhead CH42 0LQ, UK
3Arundel House, General Adult Psychiatry, Mental Health Resource Centre, Smithdown Road, Liverpool L15 2HE, UK
Correspondence to Qaiser Javed, drqaser/at/yahoo.co.uk
A 49-year-old healthy white British female, not previously known to psychiatric services, presented with an acute onset of florid psychotic symptoms. Her symptoms included visual, auditory and tactile hallucinations as well as persecutory delusions. She was started on antipsychotic medication; however, her psychotic symptoms did not improve significantly in the first 3 months. Her blood tests were normal. Lumbar puncture was performed which was positive for protein 14-3-3. A computed tomography scan of the brain showed generalised atrophic changes. The history of early visual hallucinations, rapid cognitive decline and positive 14-3-3 result was in keeping with the Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD). Despite a short life expectancy as reported in literature, our patient, who was diagnosed with sCJD more than two-and-a-half years ago, is still alive. We therefore believe this is an important finding to report.
Background
To our knowledge this is the first reported case of a newly diagnosed patient with sporadic Creutzfeldt-Jakob disease (sCJD) who presented with florid psychotic features, tonic-clonic seizures, and who was diagnosed more than two-and-a-half years ago. She is still alive despite a short life expectancy, as reported in the literature. Discussion of this case shows that clinical attitudes can lead to a misdiagnosis of CJD with other psychiatric diseases, and indicates the importance of repeating complementary investigations, even if these tests are often negative or non-specific in the early stages of CJD.
A 49-year-old unmarried, previously healthy female patient, not previously known to psychiatric services, presented with an acute onset of psychotic symptoms. Her symptoms included visual, auditory and tactile hallucinations as well as persecutory delusions.
The first symptoms started around 6 months before her hospital admission when she appeared more quiet, withdrawn and was complaining of headaches. Her condition deteriorated further before her admission. There was an episode where she appeared very confused at a local store and had to be accompanied back home. She was constantly speaking about seeing a dead body. This precipitated the involvement of the community psychiatric team which resulted in her admission. The initial impression was that she was suffering from an acute psychotic episode and as a result she was treated with olanzapine. After a few weeks it was noted that her cognitive function had started to deteriorate, mainly affecting her short term memory and concentration. She also developed three grand mal seizures within a span of 3 weeks.
Her gait started to become stooped with reduced arm swing, especially on the right hand side. There was no noticeable tremor. She did not appear to be bradykinetic but her tone was increased more so on the right hand side. The glabellar tap sign was negative. There was no suggestion of ataxia when she was walking or reaching to pick up objects. There was no suggestion of Romberg’s phenomenon.
There was no significant past medical or surgical history. She was not on any regular medication before admission. She never received any blood transfusion. There was no history of inherited neurological disease or dementia in the family, and no history of smoking, alcohol or any recreational drug abuse.
The patient was fully investigated for an organic cause of her clinical presentation. She underwent computed tomography (CT) scan of the head and electroencephalograms (EEGs) at different points during her stay on ward.
  • Baseline routine blood tests (including full blood count, erythrocyte sedimentation rate, kidney and liver function, serum copper, ceruloplasmin, VDRL and HIV test) were all normal.
  • CT scan brain showed generalised atrophic changes.
  • Cerebrospinal fluid (CSF) showed positive 14-3-3 protein.
  • Magnetic resonance imaging (MRI) of the brain showed atrophic changes.
  • EEG was non-specific.
  • Prepolarised MRI (PMRI) of the brain with WI and flare imaging showed general atrophy.
  • HIV test, autoantibody screen, and thyroid function test were all normal.
Infectious
  • HIV dementia
  • Syphilis
  • Viral encephalitis.
Toxic-metabolic
  • Endocrine abnormalities (thyroid disturbances, parathyroid abnormalities, adrenal diseases)
  • Electrolyte abnormalities (including Ca, Mg, P)
  • Vitamin deficiency (B12 (cyanocobalamin), B1 (thiamine), niacin, folate (dementia rare))
  • Wilson’s disease
  • Hepatic encephalopathy.
Autoimmune
  • Hashimoto’s encephalopathy (HE)
  • Paraneoplastic (autoimmune) limbic encephalopathy (PLE)
  • Non-paraneoplastic autoimmune (eg, anti-voltage gated potassium channel (VGKC) antibodies mediated)
  • Sarcoid.
Metastases/neoplasm
  • Non-autoimmune paraneoplastic conditions
  • Metastases to central nervous system (CNS).
Neurodegenerative
  • Prion disease
  • Alzheimer’s disease
  • Frontotemporal dementia.
Treatment
During her stay in hospital the patient was treated with olanzapine (antipsychotic) and mirtazapine (antidepressant) with limited effect initially. Her behaviour improved significantly after a few months. She was no longer responding to external stimuli, and no longer talking about seeing a dead body. She was much less agitated, and was pleasant and amenable to intervention. There was no evidence of wandering on the ward. Hence, an appropriate placement was identified and she was discharged to a residential home with 24 h care.
Outcome and follow-up
Since discharge from hospital more than one-and-a-half years ago, the patient remains asymptomatic as far as her psychotic symptoms are concerned. Although her cognitive abilities have not improved, there has not been a pronounced deterioration either. She is settled in her current care home and able to relate to her carer in a positive way, and recognises close family relatives. She continues to take olanzapine and mirtazapine and receives regular follow-up by the consultant psychiatrist and neurologist on a 3 monthly basis.
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.
Learning points
  • 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.
Footnotes
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.
REFERENCES
1. Skinningsrud A, Stenset V, Gundersen AS, et al. Cerebrospinal fluid markers in Creutzfeldt-Jakob disease. Cerebrospinal Fluid Research 2008; 5: 14. [PMC free article] [PubMed]
2. Zerr I, Pocchiari M, Collins S. Ananlysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob diasease. Neurology 2000; 55: 811–15. [PubMed]
3. Lodi R, Parchi P, Tonon C, et al. Magnetic resonance diagnostic markers in clinically sporadic prion disease: a combined brain magnetic resonance imaging and spectroscopy study. Brain 2009; 132: 2669–79. [PMC free article] [PubMed]
4. Gozke E, Erdal N, Unal M. Creutzfeldt-Jacob disease: a case report. Cases Journal 2008; 1: 146. [PMC free article] [PubMed]
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