44 research outputs found

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

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    <div><p>Background</p><p>Akinetic mutism is a key diagnostic feature of prion diseases, however, their rapidly progressive nature makes detailed investigation of the language disorder in a large cohort extremely challenging. This study aims to position prion diseases in the nosology of language disorders and improve early clinical recognition.</p><p>Methods</p><p>A systematic, prospective investigation of language disorders in a large cohort of patients diagnosed with prion diseases. 568 patients were included as a sub-study of the National Prion Monitoring Cohort. All patients had at least one assessment with the MRC Scale, a milestone-based functional scale with language and non-language components. Forty patients, with early symptoms and able to travel to the study site, were also administered a comprehensive battery of language tests (spontaneous speech, semantics, syntax, repetition, naming, comprehension and lexical retrieval under different conditions).</p><p>Results</p><p>5/568 (0.9%) patients presented with leading language symptoms. Those with repeated measurements deteriorated at a slower rate in language compared to non-language milestones. Amongst the subgroup of 40 patients who underwent detailed language testing, only three tasks–semantic and phonemic fluency and sentence comprehension–were particularly vulnerable early in the disease. These tasks were highly correlated with performance on non-verbal executive tests. Patients were also impaired on a test of dynamic aphasia.</p><p>Conclusion</p><p>These results provide evidence that the language disorder in prion disease is rarely an isolated clinical or cognitive feature. The language abnormality is indicative of a dynamic aphasia in the context of a prominent dysexecutive syndrome, similar to that seen in patients with the degenerative movement disorder progressive supranuclear palsy (PSP).</p></div

    Comparison of patients’ (n = 40) and controls’ (n = 33) mean scores on the battery of language tasks in a subset group that underwent detailed neuropsychological testing.

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    <p>Comparison of patients’ (n = 40) and controls’ (n = 33) mean scores on the battery of language tasks in a subset group that underwent detailed neuropsychological testing.</p

    The verbal component of the MRC Scale [18].

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    <p>The verbal component of the MRC Scale [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190818#pone.0190818.ref018" target="_blank">18</a>].</p

    Comparison of patients (n = 40) and controls’ (n = 33) performance on the Hayling and High/Low sentence completion tasks in a subset group that underwent detailed neuropsychological testing.

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    <p>Comparison of patients (n = 40) and controls’ (n = 33) performance on the Hayling and High/Low sentence completion tasks in a subset group that underwent detailed neuropsychological testing.</p

    RML prion infectivity following digestion with 1 mg/ml pronase E.

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    <p>10% (w/v) RML brain homogenate was incubated with pronase E (1 mg/ml at 37°C) for varying incubation times. For each time point RML prion infectivity was measured by the Scrapie Cell Assay and expressed as a percentage of total infectivity present in the untreated sample; mean ± S.E.M. (<i>n</i> = 5).</p

    Pronase E digested and NaPTA precipitated mouse brain homogenate evaluated by silver stain SDS-PAGE.

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    <p>10% (w/v) homogenates from normal CD-1 brain (CD-1) or RML prion-infected brain (RML) were either untreated (Pro −, NaPTA −), digested by pronase E at 100 µg/ml, 37°C for 30 min (Pro +, NaPTA −), precipitated by NaPTA (Pro −, NaPTA +) or sequentially digested by pronase E at 100 µg/ml, 37°C for 30 min and precipitated by NaPTA (Pro +, NaPTA +). The equivalent of 2 µl 10% (w/v) brain homogenate was loaded in each lane and the gel was stained with silver nitrate.</p

    Pronase E-resistant RML prion infectivity is precipitated by NaPTA.

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    <p>10% (w/v) homogenates from normal CD-1 brain (CD-1, white bars) or RML prion-infected brain (RML, black bars) were either untreated (whole homogenate), incubated at 37°C for 90 min and 20°C for 30 min (temperature control), digested with pronase E at 100 µg/ml, 37°C for 30 min (pronase), precipitated by NaPTA (NaPTA) or sequentially digested by pronase E at 100 µg/ml, 37°C for 30 min and precipitated by NaPTA (pronase + NaPTA). The concentration of PrP in all samples was measured by ELISA (A) and is expressed as a percentage of the total PrP present in the untreated RML samples; mean ± S.E.M. (<i>n</i> = 5). RML prion infectivity was measured by the Scrapie Cell Assay (B) and expressed as total infectivity present in the samples; mean ± S.E.M. (<i>n</i> = 5).</p

    RML prion infectivity and PrP content following digestion with PK, thermolysin or pronase E.

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    <p>10% (w/v) RML prion-infected brain homogenate was incubated at 37°C with (A) PK (50 µg/ml); (B) thermolysin (100 µg/ml) or (C) pronase E (100 µg/ml) for varying incubation times. For each time point, PrP (filled circles) was measured by ELISA and expressed as a percentage of total PrP present in the untreated sample; mean ± S.E.M. (<i>n</i> = 3, PK and thermolysin; <i>n</i> = 5, pronase E). RML prion infectivity (open circles) was measured by the Scrapie Cell Assay and expressed as a percentage of total infectivity present in the untreated sample; mean ± S.E.M. (<i>n</i> = 3, PK and thermolysin; <i>n</i> = 5, pronase E). Immunoblots of the corresponding protease and incubation time point are shown in panels to the right. Blots were probed with anti-PrP monoclonal antibody ICSM35. Apparent molecular masses are shown in kDa. Data in panels A and B have been published previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015679#pone.0015679-Cronier1" target="_blank">[25]</a>.</p
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