The language disorder of prion disease is characteristic of a dynamic aphasia and is rarely an isolated clinical feature

Caine, Diana; Nihat, Akin; Crabb, Philippa; Rudge, Peter; Cipolotti, Lisa; Collinge, John; Mead, Simon

doi:10.1371/journal.pone.0190818

Cited by 9 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with our language assessment, the patient could repeat word, not-words and sentences, but produced a reduced output, clearly showed by impaired performance on fluency tasks and spoken picture description, demonstrating an executive derangement in language tests as well as in other executive tasks (Trail Making Test, Part B, digit span backward). This is in line with a recent report that outlined that language disorders in prion diseases represent a dynamic aphasia in the context of a prominent dysexecutive syndrome (Caine et al, 2018). PET findings could be compatible with LPA even though hypometabolism was found to extend beyond the temporoparietal areas.…”

Section: Discussionsupporting

confidence: 92%

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation

Prodi

Rossi

Bertaina

et al. 2020

Front. Behav. Neurosci.

View full text Add to dashboard Cite

We describe the clinical features, neuropsychological tests, laboratory, electroencephalography (EEG), magnetic resonance imaging (MRI) and positron emission tomography (PET) findings of a 59-year-old woman who presented to our Centre for cognitive impairment since few months, with language disturbances, particularly anomia, dyscalculia, and memory loss. The clinical and neuropsychological features were non-specific and overlapping with those of other rapidly progressing neurodegenerative disorders. However, brain MRI played a pivotal role in the diagnosis, showing cortical diffusion restriction, particularly in the parietal lobes and posterior cingulum, with sparing of the perirolandic cortex, typical of Creutzfeldt-Jakob disease (CJD). Brain MRI abnormalities were visible since the first evaluation and remained stable at 2 and 6 weeks follow up. Basal ganglia and thalami were never involved. PET showed left lateralized reduced glucose metabolism, with partial overlap with MRI signal abnormalities. Despite MRI were strongly indicative of CJD, clinical, laboratory and EEG findings did not fulfill the diagnostic criteria for CJD which applied at the time of clinical assessment. Indeed, neither myoclonus, visual or cerebellar signs or akinetic mutism were present. Also, the characteristic periodic sharp wave complexes were absent at baseline EEG, and the CSF assay for 14-3-3 was negative. We, therefore, performed a real-time quaking-induced conversion (RT-QuIC) assay on a frozen sample of corticospinal fluid (CSF), which showed a positive result. RT-QuIC is a prion protein conversion assay that has shown high diagnostic sensitivity and specificity for the diagnosis of CJD. RT-QuIC has been recently incorporated in the National CJD Research and Surveillance Unit and Center for Disease Control and Prevention (CDC) diagnostic criteria for CJD. The fatal evolution of the disease brought the patient to death 13 months after symptoms onset. Pathology proved the diagnosis of sporadic CJD, subtype MM/MV 2C.

show abstract

Section: Discussionsupporting

confidence: 92%

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation

Prodi

Rossi

Bertaina

et al. 2020

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in healthy people with the inherited prion disease mutation P102L (Rudge et al, Brain 2019). We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease (Caine et al, 2015;2018). Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease.…”

mentioning

confidence: 87%

“…In the longitudinal analysis, we analysed data from twenty four patients who were presymptomatic at the time of recruitment and were followed up over a period of up to seventeen years, of whom sixteen remained healthy and eight converted to become symptomatic. In the cross-sectional analysis, the key finding was that, relative to a group of 25 healthy non-gene carrier controls, patients with subjective symptoms but without positive clinical findings were impaired on a smaller but very similar set of tests (Trail Making Test part A, Stroop Test, Performance IQ, gesture repetition, figure recall) to those previously found to be impaired in mild prion disease (Caine et al, 2015;2018). In the longitudinal analysis, Trail Making Test parts A and B, Stroop test and Performance IQ scores significantly discriminated between patients who remained presymptomatic and those who converted, even before the converters reached criteria for formal diagnosis.…”

mentioning

confidence: 92%

Cognitive decline heralds onset of symptomatic inherited prion disease

Mole

Mead

Rudge

et al. 2021

Brain

Self Cite

View full text Add to dashboard Cite

The clinical effectiveness of any disease-modifying treatment for prion disease, as for other neurodegenerative disorders, will depend on early treatment before damage to neural tissue is irrevocable. Thus, there is a need to identify markers that predict disease onset in healthy at-risk individuals. Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in individuals with the inherited prion disease mutation P102L. We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease. Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease. In the cross-sectional analysis, we analysed the performance of patients at three time points in the course of disease onset: prior to symptoms (n = 27), onset of subjective symptoms without positive clinical findings (n = 8) and symptomatic with positive clinical findings (n = 24). In the longitudinal analysis, we analysed data from 24 patients who were presymptomatic at the time of recruitment and were followed up over a period of up to 17 years, of whom 16 remained healthy and eight converted to become symptomatic. In the cross-sectional analysis, the key finding was that, relative to a group of 25 healthy non-gene carrier controls, patients with subjective symptoms but without positive clinical findings were impaired on a smaller but similar set of tests (Trail Making Test part A, Stroop test, Performance IQ, gesture repetition, figure recall) to those previously found to be impaired in mild prion disease. In the longitudinal analysis, Trail Making Test parts A and B, Stroop test and Performance IQ scores significantly discriminated between patients who remained presymptomatic and those who converted, even before the converters reached criteria for formal diagnosis. Notably, performance on the Stroop test significantly discriminated between presymptomatic patients and converters before the onset of clinical symptoms [area under the curve = 0.83 (95% confidence interval, 0.62–1.00), P = 0.009]. Thus, we report here, for the first time, neuropsychological abnormalities in healthy patients prior to either symptom onset or clinical diagnosis of inherited prion disease. This constitutes an important component of an evolving profile of clinical and biomarker abnormalities in this crucial group for preventive medicine.

show abstract

“…Notwithstanding both the variety of causes of human prion diseases and their phenotypic heterogeneity, we have previously demonstrated in a large mixed cohort that early disease is characterised by a signature pattern of cognitive deficits (Caine et al ., 2015; 2018). These comprise prominent executive impairment, parietal dysfunction, dynamic aphasia, and reduced motor speed.…”

Section: Introductionmentioning

confidence: 99%

“…Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in healthy people with the inherited prion disease mutation P102L (Rudge et al , Brain 2019). We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease (Caine et al ., 2015; 2018). Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease.…”

mentioning

confidence: 99%

Cognitive decline heralds onset of symptomatic inherited prion disease

Mole

Mead

Rudge

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The clinical effectiveness of any disease-modifying treatment for prion disease, as for other neurodegenerative disorders, will depend on early treatment before damage to neural tissue is irrevocable. Thus, there is a need to identify markers which predict disease onset in healthy at-risk individuals. Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in healthy people with the inherited prion disease mutation P102L (Rudge et al, Brain 2019). We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease (Caine et al., 2015; 2018). Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease. In the cross-sectional analysis, we analysed the performance of patients at three time points in the course of disease onset: prior to symptoms (n = 27), onset of subjective symptoms without positive clinical findings (n = 8) and symptomatic with positive clinical findings (n = 24). In the longitudinal analysis, we analysed data from twenty four patients who were presymptomatic at the time of recruitment and were followed up over a period of up to seventeen years, of whom sixteen remained healthy and eight converted to become symptomatic. In the cross-sectional analysis, the key finding was that, relative to a group of 25 healthy non-gene carrier controls, patients with subjective symptoms but without positive clinical findings were impaired on a smaller but very similar set of tests (Trail Making Test part A, Stroop Test, Performance IQ, gesture repetition, figure recall) to those previously found to be impaired in mild prion disease (Caine et al., 2015; 2018). In the longitudinal analysis, Trail Making Test parts A and B, Stroop test and Performance IQ scores significantly discriminated between patients who remained presymptomatic and those who converted, even before the converters reached criteria for formal diagnosis. Notably, performance on the Stroop test significantly discriminated between presymptomatic patients and converters before the onset of clinical symptoms (AUC = .83 (95% CI, 0.62, 1.00), p =.009). Thus, we report here, for the first time, neuropsychological abnormalities in healthy patients prior to either symptom onset or clinical diagnosis of IPD. This constitutes an important component of an evolving profile of clinical and biomarker abnormalities in this crucial group for preventive medicine.

show abstract

The language disorder of prion disease is characteristic of a dynamic aphasia and is rarely an isolated clinical feature

Cited by 9 publications

References 33 publications

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation

Report of a Case of Creutzfeldt-Jakob Disease With an Unusual Clinical Presentation

Cognitive decline heralds onset of symptomatic inherited prion disease

Cognitive decline heralds onset of symptomatic inherited prion disease

Contact Info

Product

Resources

About