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Variably protease-sensitive prionopathy (VPSPr) is a recently described neurodegenerative disorder characterised by the presence of spongiform encephalopathy and an unusual immunostaining and immunoblotting pattern for the disease-associated prion protein (PrPSc).1 This links VPSPr to human prion diseases, which are uniformly fatal disorders. The clinical symptoms and the longer duration of illness make VPSPr distinct from sporadic or idiopathic Creutzfeldt-Jakob disease (sCJD).1 Doxycycline treatment has been evaluated in patients with prion disease, however, there is little evidence that it can reverse the clinical symptoms or reduce the underlying disease progression once established.2 We present a patient with VPSPr who received doxycycline and survived for an extended period of time in an akinetic and mute state.
Neuropathological examination was performed using published methods and various anti-PrP antibodies.3 Frozen tissues from selected brain regions were available for biochemical analysis. Tissues were analysed for the presence of protease-resistant PrP (PrPres) as previously described (see online supplementary material).4
In May 2007, a registered psychiatrist suspected an organic affective disorder in a 54-year-old Austrian woman. Two months earlier, medical work-up for presumed weight loss of 16 kg within the past 18 months had been unremarkable. In June 2007, the patient was admitted to a clinic that specialised in disorders of the nervous system. Her family history was negative for neurodegenerative diseases and there was no evidence of exposure to toxins. She reported depressed mood and short-term memory problems, and difficulties with balance, walking, driving and cooking. On neuropsychological examination she was oriented to time, place, person and situation, Mini-Mental State Examination score was 22/30, clock drawing test score was 3/9. She had word-finding difficulties, ideational apraxia, acalculia and visuoconstructive deficits. She displayed affective incontinence with crying fits. She had gait ataxia, and extensor plantar responses were observed with increased tone …
Contributors HA, RT and JT reviewed the clinical data, EEGs and neuroradiological images, wrote portions of the manuscript and revised and edited the manuscript. MWH, HY and JWI performed immunoblotting and neuropathological studies and wrote portions of the manuscript and revised and edited the manuscript. SW was involved in the neuropathological assessment and revised the manuscript. TS was involved in the genetic analysis and revised the manuscript. FA-D, RH, HB and JR were involved in the follow-up of the patient and revised the manuscript. GGK coordinated the study, wrote significant portions of the manuscript, and revised and edited the manuscript.
Funding The NCJDRSU is funded by the Policy Research Programme of the Department of Health, and by the Scottish Government (DH121/5061). Edinburgh Brain Banks is supported by the Medical Research Council (MRC G0900580). The Austrian Reference Center for Human Prion Diseases (OERPE) is supported by the Austrian Federal Ministry of Health (BMG).
Competing interests JR and GGK report grants from Austrian Federal Ministry of Health (BMG), during the conduct of the study; GGK reports grants from EU FP7 Project Develage, outside the submitted work. JWI reports grants from Department of Health, London, grants from Medical Research Council, personal fees and non-financial support from Piramal, personal fees from Covance, personal fees and non-financial support from Springer, outside the submitted work.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.