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Case Reports
, 82 (23), 2107-11

Gerstmann-Straüssler-Scheinker Disease: Novel PRNP Mutation and VGKC-complex Antibodies

Case Reports

Gerstmann-Straüssler-Scheinker Disease: Novel PRNP Mutation and VGKC-complex Antibodies

Matthew Jones et al. Neurology.


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.


Figure 1
Figure 1. Postmortem histopathology
(A) Multicentric amyloid plaques (center) were present in the cerebral cortex in the absence of spongiform change. Hematoxylin & eosin stain, ×400. (B) Immunohistochemistry for prion protein shows extensive deposition in the cerebellum in the form of multicentric plaques, smaller plaque-like deposits, and diffuse deposits (brown). Occasional plaques are also present in the subcortical white matter (upper left). KG9 anti-prion protein antibody with hematoxylin counterstain, ×50.
Figure 2
Figure 2. Western blot analysis
Western blot analysis of a 10% weight-to-volume frontal cortex brain homogenate from this case (lanes 2, 4, 6, and 8). Individual lanes were loaded with 5 μL without prior digestion with proteinase K (lane 2), 5 μL after digestion with proteinase K (lane 4), 0.5 μL after digestion with proteinase K (lane 6), and 50 μL after digestion with proteinase K and collection of PrPres by centrifugation (lane 8). These were compared with reference standards of 10% weight-to-volume frontal cortex brain homogenates from cases of sporadic Creutzfeldt-Jakob disease (CJD) MM1 subtype (lanes 3 and 7), variant CJD (lanes 5 and 9), and sporadic CJD VV2 subtype (lane 10). Molecular mass standards of 40, 30, and 20 kDa can be seen in lane 1. Panel A is a short (30-second) exposure, whereas panel B is a maximal exposure (30 minutes).

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