Case report of Lewy body disease mimicking Creutzfeldt-Jakob disease in a 44-year-old man

We report the case of a young patient with confirmed DLB that did not fulfil the revised clinical criteria [3] (see Table 2). Global cognitive impairment was indeed acute at onset, while progressive impairment is a mandatory requirement for DLB diagnosis. Moreover, no fluctuating cognition was observed during follow-up, while 75 % of DLB patients experience such fluctuations, which are a core feature of typical DLB [6]. Our patient also experienced slight visual hallucinations for one year, in a context of severe paranoid delusion without neuroleptic sensitivity, while delirium duration is usually short in DLB [7]. Moreover, hallucinations may also occur in CJD [8].

Early diagnostic profile of the case according to the revised criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) – adapted from McKeith et al., Neurology 2005 [3]

Probable DLB Two core features or one core feature and one or more suggestive features, Possible DLB Up to one core feature and one or more suggestive features

Features for Creutzfeldt-Jakob disease are adapted from the MRI-CJD Consortium criteria for sporadic Creutzfeldt–Jakob disease [8]

The patient’s clinical presentation was similar to the cognitive subtype of CJD described by Puoti et al. [9], with acute dementia, confusion and cortical visual disturbance, extrapyramidal signs and myoclonus. Although MRI did not show diffusion abnormalities, such clinical presentation and positive 14.3.3 protein detection were consistent with CJD diagnosis [8]. Cases of DLB are reported in neuropathological series of suspected CJD [4, 10–12]. But in these series, patients are at least 60 years-old; symptomatic progression is rapid and leads to death within one to two years. Despite an acute onset, our 44-year-old patient showed a clinical progression and disease duration similar to usual DLB [13], and no longer fulfilled the clinical criteria for sporadic CJD disease [8] two years later.

Interestingly, patients suspected for CJD during lifetime but with confirmed DLB at autopsy often share myoclonus, pyramidal and extrapyramidal symptoms [10]. While fluctuating cognition and repeated falls are rare, hallucinations and akinetic mutism are variable among the series. When performed, 14–3–3 protein detection is negative in most cases, except for Van Everbroeck and colleagues who reported rare 14–3–3 protein positivity (less than 20 % of definite DLB) [14]. Of note, a recent study presented tau protein levels as a better marker than 14–3–3 protein in the diagnosis of CJD [15]. After 2 years of clinical evolution, CSF total tau level was within the normal range, confirming the hypothesis that our patient had no CJD.

As observed in our case, none of the previously reported confirmed LBD patients with suspicion of CJD had cerebellar symptoms, or hypersignal on MRI, but most of them had diffuse cortical atrophy [10]. Regarding our patient, comparison to a control population revealed a wide bilateral atrophy involving all cortical regions, as well as subcortical nuclei such as the putamen and the pallidum. Decrease of grey matter density in the insula and the putamen has been recently reported as a characteristic pattern of atrophy in patients with DLB [16]. This pattern should also include lateral temporal atrophy, but we reported a broader pattern of atrophy, including other cortical regions. This extended atrophy suggests an advanced stage of the pathology in the patient’s brain, although the MRI used was performed soon after clinical onset.

The patient also presented with widespread cortical hypometabolism, sparing orbitofrontal regions as well as posterior cingulate and thalamus. Interestingly, we found bilateral hypermetabolism in the posterior part of the putamen. To our knowledge, this is the first report of striatal hypermetabolism in DLB [17]. Compensatory mechanisms may explain this finding, but further investigations are required.

While mean age of onset for DLB is usually 75 years old, ranging from 50 to 80, DLB can also be an uncommon cause of dementia in young patients [18]. Few patients have been reported with DLB before 50 years-old [2]. Most of them were reported in Japan [19], although they did not fulfill the revised criteria for DLB, and may not have had pure DLB [20]. Because our case was sporadic and because parkinsonism was the core clinical feature, molecular genetic analysis was limited to the alpha synuclein and prion protein genes. However, other genetic variations were also reported in DLB [21]. In this case, the implication of these other genes is unlikely, considering the pathological findings of Lewy bodies and Lewy neurites without beta amyloid plaques or widespread neurofibrillary tangles.

In summary, our case illustrates that DLB can occur in young patients with an atypical and severe clinical presentation, which can first be mistaken for CJD. Laboratory and neuroimaging investigations are useful to exclude systemic and pharmacological causes of delirium and cognitive impairment, but remain insufficient to allow an accurate diagnostic of DLB, particularly in young patients. Specific markers to support such diagnosis are needed.