Background: 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.
Methods: 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).
Results: 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.
Conclusion: 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).