Identification of Creutzfeldt-Jakob Disease Variants—Reply

The recent article by Appleby et al¹ demonstrated an interesting phenotypic classification of sporadic Creutzfeldt-Jakob disease (sCJD). Of particular note were the characteristics of patients with the affective variant, who reported psychiatric symptoms in the first week of illness. These individuals also experienced the longest median survival time of all phenotypes (421 days). Interestingly, the early psychiatric presentation and prolonged survival of affective cases are reminiscent of variant CJD (vCJD), an entity associated with an exposure to the agent carrying bovine spongiform encephalopathy.² Although nearly all vCJD cases have emerged in Europe and demonstrate distinct clinical features (including a mean age at onset in the third decade of life), these similarities and additional data presented by Appleby and colleagues do raise concern about our ability to promptly diagnose vCJD in the United States. In particular, the patients with the affective variant experienced the longest median duration of illness until clinical presentation (92 days) and subsequently underwent diagnostic testing far later from the time at onset than those with other phenotypes. The median intervals from disease onset to lumbar puncture for 14-3-3 protein analysis and brain magnetic resonance imaging were 222 and 232 days, respectively.¹ Therefore, the duration until clinical diagnosis of CJD was presumably longer.

Even in the United Kingdom, where nearly 80% of vCJD cases have been identified since the condition was first recognized in 1996 (and where the mean interval between the onset of symptoms and diagnosis decreased by an average of 4% annually), the delay to diagnosis was still an estimated 9 months in 2005.³ Since all three American vCJD cases to date have demonstrated a history consistent with an exposure abroad,⁴ I wonder how long it might take to diagnose a vCJD case less likely to arouse our suspicion but with potentially far greater consequences for the public health: an American citizen with a native exposure and no history of foreign travel. Given the relatively recent identification of cattle with bovine spongiform encephalopathy on American soil,⁵ such a scenario is not unimaginable. However, further emphasis on the phenotypic features of CJD proposed by Appleby and colleagues may also lead to a more timely diagnosis in this circumstance, potentially minimizing public exposure. An active effort to both educate clinicians about CJD phenotypes and involve them in improving the diagnostic process can make this goal more attainable.

Correspondence: Dr Barash, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (jbarash@bidmc.harvard.edu).

Financial Disclosure: None reported.