Findings In Creutzfeldt-Jakob Disease Research Articles

Editors' note: Teaching NeuroImages: DWI and EEG findings in Creutzfeldt-Jakob disease

In “Teaching NeuroImages: DWI and EEG findings in Creutzfeldt-Jakob disease,” Ganesh et al. described a patient with rapidly progressive dementia who was found to have lateralized periodic discharges and cortical ribboning that was more right than left, which they concluded was consistent with Creutzfeldt-Jakob disease (CJD). Drs. Yuan and Hu commented that while these findings are sufficient to diagnose sporadic CJD, neuropathology or 14-3-3 CSF results would help clarify whether this was familial CJD, iatrogenic CJD, or a new variant of CJD. Drs. Ganesh and Yeung replied that they did not pursue further testing because their patient met the diagnostic criteria for probable CJD, and that establishing a diagnosis of definite CJD would require neuropathology or immunohistochemistry results consistent with CJD or positive real-time quaking-induced conversion assay. In “Teaching NeuroImages: DWI and EEG findings in Creutzfeldt-Jakob disease,” Ganesh et al. described a patient with rapidly progressive dementia who was found to have lateralized periodic discharges and cortical ribboning that was more right than left, which they concluded was consistent with Creutzfeldt-Jakob disease (CJD). Drs. Yuan and Hu commented that while these findings are sufficient to diagnose sporadic CJD, neuropathology or 14-3-3 CSF results would help clarify whether this was familial CJD, iatrogenic CJD, or a new variant of CJD.

Author response: Teaching NeuroImages: DWI and EEG findings in Creutzfeldt-Jakob disease.

We thank Drs. Yuan and Hu for their comments on our article.1 We agree that CSF testing for prions, particularly the real-time quaking-induced conversion assay (RT-QuiC), which is superseding 14-3-3 as the test of choice in many centers, can be helpful in confirming the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) in suspected cases.2 We did not pursue such testing in our patient. She already met the proposed updated diagnostic criteria for probable CJD based on having rapidly progressive dementia (criterion A); myoclonus, cerebellar signs, extrapyramidal signs (3 of the B criteria, only 2 required); EEG periodic sharp discharges and MRI diffusion-weighted imaging abnormalities in caudate and putamen (2 of the C criteria, only 1 required); and no indication of an alternative diagnosis on routine investigations (criterion D; however, some may consider CSF to be an important routine investigation, though it carries safety risks in suspected prion disease). Nevertheless, to establish the diagnosis of definite CJD, as Drs. Yuan and Hu indicated, prion disease would need to be identified by standard neuropathologic or immunocytochemical techniques, or positive RT-QuiC of CSF or nasal brushings.

Reader response: Teaching NeuroImages: DWI and EEG findings in Creutzfeldt-Jakob disease.

We read with interest the Resident & Fellow Teaching NeuroImage by Ganesh et al.1 of a patient with Creutzfeldt-Jakob disease (CJD) presenting with rapidly progressive dementia, predominant clinical features, MRI findings of hyperintensity of the cortex and bilateral basal ganglia, and EEG (triphasic morphology). We agree with the diagnosis according to the updated clinical diagnostic criteria for sporadic CJD.2 However, it is important to provide the data on whether this patient underwent biopsy for neuropathology or if 14-3-3 protein was detected in the CSF, in order to distinguish from familial, new variant, or iatrogenic CJD. The evidence-based guideline with Level B recommendations indicated that, for patients who have rapidly progressive dementia and are strongly suspected of having sporadic CJD (sCJD), the assays for CSF 14-3-3 protein are probably moderately accurate in diagnosing sCJD.3 Despite the unavailable biopsy, the detection of protease-resistant prion by neuropathology could be helpful to the diagnosis of definite sCJD. Further studies are needed to confirm the 2015 updated diagnostic criteria for CJD in clinical practice.4

A Crertzfeldt-jakob disease case presenting with psychiatric symptoms

Creutzfeldt Jakob Disease is an incurable and invariably fatal degenerative brain disease. Sporadic and variant forms of the disease can be observed among patients. We report on a patient for calling attention to clinical features and laboratory findings of Creutzfeldt-Jakob Disease and the psychiatric prodromal symptoms. This case demonstrates that manic symptoms may also be a presenting symptom of Creutzfeldt-Jakob Disease and this diagnosis should be considered when there is rapid deterioration in cognition is observed with presence of psychiatric and neurological symptoms

Sporadic CJD (VV2 Type) Presenting with Central Vestibular Abnormalities (P03.259)

Objective: To demonstrate that Creutzfeldt-Jakob Disease (CJD) VV2 may present with only isolated ataxia on exam and to discuss abnormal neuro-vestibular testing in its relation to CJD and other CNS disorders. Background CJD is a rare and invariably fatal neurodegenerative disorder associated with abnormal accumulation of the protease resistant form of the prion protein in the central nervous system. Sporadic CJD (sCJD) is idiopathic and accounts for 80-85% of prion disease. Classically, sCJD has been known for its triad of progressive dementia, generalized myoclonus, and periodic sharp and slow wave complexes on EEG. sCJD VV2 is the second most frequent genotype accounting for around 16% of cases of sCJD. Design/Methods: Case report of a 76 year old female who presented to Ohio State University Medical Center with ataxia of unknown etiology found to have Sporadic Creutzfeldt-Jakob Disease VV2. Results: Patient had normal labs and imaging including a MRI Brain and PET Scan. She had abnormal neurovestibular testing suggestive of a CNS process. Patient also underwent Lumbar Puncture that was unremarkable except for elevated Neuron Specific Enolase, a positive 14-3-3 protein and elevated tau protein of 6378 pg/ml. Subsequent pathology on autopsy confirmed the diagnosis of Sporadic Creutzfeldt-Jakob Disease VV2. Conclusions: CJD VV2 can present with normal imaging including Brain MRI and PET scan, without the classic findings of CJD and with only isolated ataxia on exam. It is therefore of utmost importance for clinicians to remember that a lumbar puncture may be indicated in cases of isolated ataxia of unknown etiology to rule out sCJD VV2. In addition, abnormal neurovestibular testing was found to be an initial presenting abnormality in this case. Further studies on the importance of neurovestibular testing in cases of CJD and other Central Nervous System disorders may be warranted. Disclosure: Dr. Mandel has nothing to disclose. Dr. Oas has received personal compensation for activities with GlaxoSmithKline, Inc. as a speaker.

Discordance of motion artifacts on magnetic resonance imaging in Creutzfeldt-Jakob disease: comparison of diffusion-weighted and conventional imaging sequences

Motion artifact is problematic in the diagnosis of Creutzfeldt-Jakob disease (CJD) because of dementia. The purpose was to compare the occurrence of this artifact between a diffusion-weighted (DW) magnetic resonance (MR) imaging sequence and conventional sequences. Ten MR examinations comprising T2-weighted, T1-weighted, DW, and fluid-attenuated inversion recovery imaging in seven CJD patients were retrospectively evaluated. The occurrence of motion artifacts on each sequence were assessed, and the examination was classified into four groups as follows: group A, motion artifact not revealed on DW imaging but revealed on one or more other sequences; group B, revealed on DW imaging and one or more other sequences; group C, not revealed on any sequences; and group D, revealed on DW imaging but not on any other sequences. The 10 MR examinations were classified as eight group A (80%), one B (10%), one C (10%), and zero D (0%). Motion artifacts are likely to occur in any conventional imaging sequences in CJD, but the fast-imaging ability of DW imaging can reduce this artifact. The combination of an absence of motion artifact on DW imaging and the presence on conventional sequences may be one of the frequent findings of CJD.

Clinical findings in Creutzfeldt-Jakob disease mimicking dementia with Lewy bodies

Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy or prionic disease characterized by accumulation of abnormal prionic protein (PrPsc) associated to spongiform degeneration of the brain1. Although rare, CJD is the most common prionic disease in humans with an incidence rate around 1/1,000,0002. Historically, it was first described as a dementing illness by Jakob in 19213-5 […] Clinical findings in Creutzfeldt-Jakob disease mimicking dementia with Lewy bodies

Psychiatric and neuroimaging findings in Creutzfeldt-Jakob disease.

Although Creutzfeldt-Jakob disease (CJD) is the prototypical rapidly progressive dementia, clinical heterogeneity in the disease can make diagnosis difficult. Creutzfeldt-Jakob disease affects multiple brain areas, which causes multifocal deficits that involve movement, cognition, and psychiatric status. Thorough neurologic, cognitive, and psychiatric examinations are necessary for observing its clinical features. Recent advances in neuroimaging techniques have allowed researchers and clinicians to discover imaging patterns that distinguish CJD from other neurologic diseases. This article discusses how these advances may make neuroimaging the most valuable noninvasive tool for diagnosing CJD, which helps to track the progression of the disease course and provides insight into clinical-anatomic correlations.

Clinical findings in sporadic Creutzfeldt-Jakob disease correlate with thalamic pathology.

The pathogenesis underlying the typical findings in Creutzfeldt-Jakob disease (CJD) such as periodic EEG changes or myoclonus is not fully understood. The thalamus possesses a high density of inhibitory neurones and serves as a crucial pacemaker of rhythmic EEG activity. As inhibitory neurones expressing parvalbumin (PV) are reduced in the cerebral cortex and hippocampus in sporadic CJD (sCJD), we studied the distribution and number of PV-immunoreactive neurones in sCJD thalami in order to determine whether damage to them could account for certain clinical findings. Immuno histochemical analysis was performed on the thalami from 21 sCJD patients and five controls. The number of PV+ neurones was counted in the thalamic nuclei and compared with clinical and molecular findings. In sCJD patients, PV+ neurones were significantly reduced in the ventrolateral posterior (VLp), ventrolateral anterior (VLa), anteroventral (AV), lateral dorsal (LD), mediodorsal (MD) and reticular (Re) thalamic nuclei (P < 0.05). The VLp was especially damaged in sCJD patients with homozygosity for methionine at codon 129 and scrapie prion protein (PrP(Sc)) type 1. Patients with typical EEG changes [periodic sharp wave complexes (PSWCs)] and myoclonus had a predominant loss of PV+ cells in the reticular thalamic nucleus. In conclusion, our data support the hypothesis that the damage to PV-immunoreactive neurones determines the generation of certain typical clinical features of CJD, i.e. PSWCs associated with myoclonus.