Matthew Jones1, Sola Odunsi1, Daniel du Plessis1, Angela Vincent1, Matthew Bishop1, Mark W Head1, James W Ironside1, David Gow2. 1. From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK. 2. From the Greater Manchester Neurosciences Centre (M.J., D.d.P., D.G.), Salford Royal Foundation Trust, Salford; Manchester Medical School (S.O., D.d.P.), and Institute of Brain, Behaviour and Mental Health (M.J.), University of Manchester; Nuffield Department of Clinical Neurosciences (A.V.), John Radcliffe Hospital, University of Oxford; and National Creutzfeldt-Jakob Disease Research and Surveillance Unit (M.B., M.W.H., J.W.I.), University of Edinburgh, UK. dg28.2.02@live.co.uk.
Abstract
OBJECTIVE: To describe a unique case of Gerstmann-Straüssler-Scheinker (GSS) disease caused by a novel prion protein (PRNP) gene mutation and associated with strongly positive voltage-gated potassium channel (VGKC)-complex antibodies (Abs). METHODS: Clinical data were gathered from retrospective review of the case notes. Postmortem neuropathologic examination was performed, and DNA was extracted from frozen brain tissue for full sequence analysis of the PRNP gene. RESULTS: The patient was diagnosed in life with VGKC-complex Ab-associated encephalitis based on strongly positive VGKC-complex Ab titers but no detectable LGI1 or CASPR2 Abs. He died despite 1 year of aggressive immunosuppressive treatment. The neuropathologic diagnosis was GSS disease, and a novel mutation, P84S, in the PRNP gene was found. CONCLUSION: VGKC-complex Abs are described in an increasingly broad range of clinical syndromes, including progressive encephalopathies, and may be amenable to treatment with immunosuppression. However, the failure to respond to aggressive immunotherapy warns against VGKC-complex Abs being pathogenic, and their presence does not preclude the possibility of prion disease.
OBJECTIVE: To describe a unique case of Gerstmann-Straüssler-Scheinker (GSS) disease caused by a novel prion protein (PRNP) gene mutation and associated with strongly positive voltage-gated potassium channel (VGKC)-complex antibodies (Abs). METHODS: Clinical data were gathered from retrospective review of the case notes. Postmortem neuropathologic examination was performed, and DNA was extracted from frozen brain tissue for full sequence analysis of the PRNP gene. RESULTS: The patient was diagnosed in life with VGKC-complex Ab-associated encephalitis based on strongly positive VGKC-complex Ab titers but no detectable LGI1 or CASPR2 Abs. He died despite 1 year of aggressive immunosuppressive treatment. The neuropathologic diagnosis was GSS disease, and a novel mutation, P84S, in the PRNP gene was found. CONCLUSION: VGKC-complex Abs are described in an increasingly broad range of clinical syndromes, including progressive encephalopathies, and may be amenable to treatment with immunosuppression. However, the failure to respond to aggressive immunotherapy warns against VGKC-complex Abs being pathogenic, and their presence does not preclude the possibility of prion disease.
Authors: Christian G Bien; Angela Vincent; Michael H Barnett; Albert J Becker; Ingmar Blümcke; Francesc Graus; Kurt A Jellinger; David E Reuss; Teresa Ribalta; Jürgen Schlegel; Ian Sutton; Hans Lassmann; Jan Bauer Journal: Brain Date: 2012-04-25 Impact factor: 13.501
Authors: K McKnight; Y Jiang; Y Hart; A Cavey; S Wroe; M Blank; Y Shoenfeld; A Vincent; J Palace; B Lang Journal: Neurology Date: 2005-12-13 Impact factor: 9.910
Authors: Jon A Beck; Mark Poulter; Tracy A Campbell; Gary Adamson; James B Uphill; Rita Guerreiro; Graham S Jackson; James C Stevens; Hadi Manji; John Collinge; Simon Mead Journal: Hum Mutat Date: 2010-07 Impact factor: 4.878
Authors: Mark W Head; Helen M Yull; Diane L Ritchie; Jan P Langeveld; Nicholas A Fletcher; Richard S Knight; James W Ironside Journal: Brain Date: 2013-04 Impact factor: 13.501
Authors: Sarosh R Irani; Andrew W Michell; Bethan Lang; Philippa Pettingill; Patrick Waters; Michael R Johnson; Jonathan M Schott; Richard J E Armstrong; Alessandro S Zagami; Andrew Bleasel; Ernest R Somerville; Shelagh M J Smith; Angela Vincent Journal: Ann Neurol Date: 2011-03-17 Impact factor: 10.422
Authors: Simon Mead; Mark Poulter; Jon Beck; Thomas E F Webb; Tracy A Campbell; Jacqueline M Linehan; Melanie Desbruslais; Susan Joiner; Jonathan D F Wadsworth; Andrew King; Peter Lantos; John Collinge Journal: Brain Date: 2006-09 Impact factor: 13.501
Authors: Ross W Paterson; Michael S Zandi; Richard Armstrong; Angela Vincent; Jonathan M Schott Journal: J Neurol Neurosurg Psychiatry Date: 2013-06-11 Impact factor: 10.154
Authors: Mee-Ohk Kim; Leonel T Takada; Katherine Wong; Sven A Forner; Michael D Geschwind Journal: Cold Spring Harb Perspect Biol Date: 2018-05-01 Impact factor: 10.005
Authors: Leonel T Takada; Mee-Ohk Kim; Ross W Cleveland; Katherine Wong; Sven A Forner; Ignacio Illán Gala; Jamie C Fong; Michael D Geschwind Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2017-01 Impact factor: 3.568