Serial changes in regional cerebral blood flow in Gerstmann–Sträussler–Scheinker disease caused by a Pro-to-Leu mutation at codon 105 in the prion protein gene

ABSTRACT

Gerstmann–Sträussler–Scheinker disease with a Pro-to-Leu substitution at codon 105 in the prion protein gene (GSS-P105L) is a rare variant of human genetic prion disease. Herein, we report the case of a patient with GSS-P105L, who showed serial changes in regional cerebral blood flow (rCBF) on single-photon emission computed tomography (SPECT). A 42-year-old woman, with an affected father presenting with similar symptoms, had a 1-year history of progressive gait disturbance, lower-limb spasticity, and psychiatric symptoms. Genetic analysis confirmed the diagnosis of GSS-P105L. Eleven months after disease onset, brain magnetic resonance imaging (MRI) showed bilateral frontal lobe-dominant cerebral atrophy without hyperintensity on diffusion-weighted imaging (DWI) sequences; meanwhile, SPECT revealed non-specific mild hypoperfusion. Follow-up MRI at 52 months after onset demonstrated progressive frontal lobe-dominant cerebral atrophy without hyperintensity on DWI, while SPECT revealed a marked decrease in rCBF in the bilateral right-dominant frontal lobe. Patients with GSS with a Pro-to-Leu substitution at codon 102 (GSS-P102L) have been reported to exhibit hyperintensity on DWI-MRI and a diffuse decrease in CBF with a mosaic-like pattern on SPECT, which is absent in patients with GSS-P105L, thereby possibly reflecting the differences in pathophysiology between GSS-P102L and GSS-P105L.

KEYWORDS:

• Gerstmann–Sträussler–Scheinker disease
• GSS-P102L
• GSS-P105L
• MRI
• PrPSc
• SPECT
• spongiform changes

Acknowledgments

The authors are grateful to the members of the Japanese Prion Disease Surveillance Committee. We also would like to thank the members of the Department of Neurology and Neurological Science, Tokyo Medical and Dental University Hospital. We thank the patient for granting permission to publish this information.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical statement

The protocol followed all ethical requirements and was approved by the Institutional Ethics Committee of the Tokyo Medical and Dental University (ID: G2000–141). Written informed consent was obtained from the patient.

Author contributions

HK drafted and revised the article for content, including medical writing for content, and acquired the data. TM revised the article for content and acquired the data. TY supervised the study. NS revised the article, conceived of and designed the study, supervised the study, and managed the patient.

Additional information

Funding

This work was partly supported by a Grant-in-Aid from the Research Committee of Prion Disease and Slow Virus Infection of the Ministry of Health, Labour, and Welfare of Japan (NS), and a Grant-in-Aid from the Research Committee of Surveillance and Infection Control of Prion Disease of the Ministry of Health, Labour, and Welfare of Japan (NS).