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Treatable Dementias Mistaken for CJD

A retrospective analysis finds that many cases of treatable dementias may be misdiagnosed as sporadic Creutzfeldt-Jakob disease.

The diagnosis of rapidly progressive dementias (RPDs) can be difficult, as patients frequently present with a quickly evolving multitude of symptoms (Neurol Clin 2007; 25:783). Most neurologists are familiar with the presentation of the prototypical RPD, Creutzfeldt-Jakob disease (CJD), but often other etiologies either are not considered or are overlooked. In this study, researchers retrospectively assessed the nonprion pathological diagnoses of patients referred for suspected prion disease to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University from 2006 through 2009, focusing particularly on potentially treatable dementias. Referring physicians provided medical records.

Of 1106 patients' brain autopsy samples tested, about one third did not show prion disease, and approximately one quarter (71) of these showed potentially treatable disorders, including immune-mediated neurological disorders, neoplasms (e.g., central nervous system lymphoma), infections, and metabolic disorders. More than 50% of those with treatable dementias had a positive cerebrospinal fluid (CSF) 14-3-3 test recorded in their medical record.

Comment: Although all cases were referred to the NPDPSC, CJD or other prion diseases were likely not high on the referring physician's differential in many cases, for a variety of reasons. The medical records provided to the NPDPSC were not complete in all instances. Nevertheless, these cases are informative, because they exemplify nonprion etiologies for RPDs. More importantly, a subset of the disorders was treatable. This work largely corroborates the findings of other studies regarding treatable diagnoses mistaken for CJD (Neurol Clin 2007; 25:783 and Brain 1999; 122 [Pt 12]:2345), but as the authors note it also adds a few new entities (some treatable) to the possible differential of RPDs, including several infectious meningoencephalitides, hereditary diffuse leukoencephalopathy with spheroids, adult-polyglucosan body disease, Marchiafava-Bignami disease, superficial siderosis of the central nervous system, and even Huntington disease. In reality, however, it would be unlikely that some of these conditions should be mistaken for sporadic CJD clinically.

Several important clinical messages can be taken from this tour-de-force report:

1) Assessment of an RPD requires an organized, thorough approach to avoid premature diagnosis of prion disease.

2) Treatable causes of RPD must always be considered and ruled out when applicable.

3) Many patients in this report were apparently erroneously thought to have CJD or referred to the NPDPSC because tests for certain CSF biomarkers, such as the controversial 14-3-3 test, were positive — showing the danger in relying heavily on this test, when others, such as diffusion-weighted magnetic resonance imaging, are much better for CJD diagnosis (Neurology 2011; 76:1711).

— Michael D. Geschwind, MD, PhD

Dr. Geschwind is Associate Professor of Neurology, University of California, San Francisco.

Published in Journal Watch Neurology November 22, 2011

Citation(s):

Chitravas N et al. Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease. Ann Neurol 2011 Sep; 70:437.

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