Sporadic Creutzfeldt-Jakob disease: clinical and diagnostic characteristics of the rare VV1 type

Background: Creutzfeldt-Jakob disease (CJD) is a rare and fatal disease caused by prions. Recently, 6 molecular subtypes of sporadic CJD (sCJD) have been identified showing differences regarding the disease course, neuropathological lesion patterns and sensitivity to diagnostic tools. In the literature, only isolated cases of the rare VV1 subtype have been reported so far. We describe the clinical characteristics and neuropathological lesion profiles in 9 of our cases and review the literature on former VV1 case reports.

Methods: In the years 1993 until late 2003, 571 definite neuropathologically confirmed cases of sporadic CJD were identified in Germany. Of these, 9 were homozygous for valine and displayed type 1 of the pathological PrPSc in the brain (VV1 subtype).

Results: We describe 8 males and only one female belonging to the VV1 subtype. All patients were relatively young at disease onset (median 44 years vs. 65 years in all sCJD) with prolonged disease duration (median 21 months vs. 6 months in all sCJD). During the initial stages, their main clinical signs were personality changes and slowly progressive dementia as well as focal neurological deficits. The latter matched the MRI and EEG findings. None of the 9 VV1 patients had periodic sharp-wave complexes (PSWCs) in the EEG. Only 2 out of 7 displayed the typical signal increase of the basal ganglia on MRI, whereas signal increase of the cortex was seen in all patients. The 14–3-3 protein could be found in all cases tested.

Discussion: It should be noted that a small group of sporadic CJD patients with the VV1 subtype may present with an atypical disease course at an early age. Thus, the new variant of CJD (vCJD) is sometimes suspected. MRI plays an important role in differentiating these two disease types and should be performed early during the disease course.