Variant Creutzfeldt-Jakob Disease: A Review of 150 Cases

Abstract & Commentary

By John J. Caronna, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Caronna reports no financial relationships relevant to this field of study.

Synopsis: Variant Creutzfeldt-Jakob disease usually presents with subtle psychiatric symptoms and there is usually a significant delay in diagnosis.

Source: Heath CA, et al. Diagnosing variant Creutzfeldt-Jakob disease: A retrospective analysis of the first 150 cases in the U.K. J Neurol Neurosurg Psychiatry 2011;82:646-651

In the mid-1990s, variant Creutzfeldt-Jakob disease (vCJD) was recognized as an example of bovine-to-human spread of bovine spongiform encephalopathy (mad cow disease) by ingestion of meat products infected with the pathogenic prion protein. At present, more than 200 probable cases of vCJD have been identified in 11 countries.1 In all patients, infection occurred either during residence in the UK or through contact with meat products, animals, or animal products exported from the UK. Four cases of vCJD transmitted by blood transfusion have been reported.2

The authors undertook a retrospective study of the first 150 cases of vCJD identified in the UK between 1995 and 2005. They systematically analyzed symptoms, signs, and the diagnostic process with the aim of achieving an earlier diagnosis in future cases of vCJD.

In this series, individuals with vCJD rarely sought medical attention early in the clinical course. The median time from onset to first medical contact was 2.5 months (mean 3.4 months). Early clinical features of vCJD were subtle and of insidious onset. Non-specific psychiatric symptoms — anxiety, irritability, social withdrawal, agitation, and insomnia — dominated the early clinical course. Neurologic features developed early in only a minority of patients, were usually non-specific symptoms such as painful dysesthesias, and were not associated with an abnormal neurological examination. Patients with neurological features or a combination of neurological and psychiatric symptoms presented earlier to a medical practitioner, in comparison with those who had only psychiatric features: neurological onset, 2 months; psychiatric onset, 3.3 months; and combined neurologic and psychiatric symptoms, 1.7 months. At first medical contact, vCJD was not considered as a possible diagnosis in any patient.

The mean time from onset to neurological referral was 7.4 months. In 147 of 150 cases, the mean time from onset to suspected diagnosis of vCJD was 8.9 months and to confirmed diagnosis by current diagnostic criteria (see article) was 10.5 months. In two older patients aged 68 and 74 years not diagnosed in life, vCJD was identified at autopsy. In one case detailed information was not available.

Thirty-eight patients diagnosed within 6 months of onset had both a more rapidly progressive course and earlier objective neurologic signs, which probably led to the earlier diagnosis.

Brain MRI supported the clinical diagnosis of vCJD in 143 of 150 patients. The majority of the negative MRI scans did not include the fluid attenuated inversion recovery (FLAIR) sequence that is most sensitive for identifying hyperintensity of the pulvinar and thalamus that is characteristic of vCJD.

The authors conclude that achieving an early diagnosis of vCJD remains a challenge because of the insidious onset of illness, and the non-specific and mainly psychiatric early clinical features in the majority of cases.

Commentary

There is no effective treatment of vCJD whether diagnosed early or late in the clinical course. Fortunately, the number of clinically recognized cases of vCJD is declining: nevertheless, the possibility of unidentified environmental reservoirs for prions in soil and in animals other than cattle suggests that eradication of the disease may not be possible.1

Although a diagnosis of vCJD early in the clinical course has little therapeutic benefit for the affected individual, the public health implications of delayed diagnosis are serious. In the present series, 18 patients had 20 surgical procedures after the onset of illness and before vCJD was diagnosed. Four affected individuals donated blood in the early clinical phase of illness. It is unknown whether secondary transmission of vCJD by contaminated surgical instruments and donated blood occurred. The authors have provided an excellent review of the clinical features of vCJD and have underscored the need for clinicians to consider the diagnosis in patients, young or old, presenting with a progressive neuropsychiatric disorder.

References

1. Up to Date. Variant-Creutzfeldt-Jacob disease. Available at: www.uptodate.com. Accessed June 16, 2011.

2. Fourth case of transfusion associated variant-CJD infection. Health Protection Report 2007;1. Available at: www.hpa.org.UK. Accessed June 16, 2011.