RESUMEN
Gerstmann-Sträussler-Scheinker syndrome (GSS) is an autosomal dominant neurodegenerative disease caused by point mutations in the prion protein gene (PRNP). While variable, the clinical presentation typically encompasses progressive cerebellar ataxia, pyramidal signs, and cognitive impairment. Here, we report a case of F198S-associated GSS manifesting levodopa-responsive parkinsonism, levodopa-induced dyskinesia, and an abnormal (I-123)-FP-CIT single-photon emission computed tomography (DaT-SPECT). A 66-year-old male patient presented with six years of progressive recall and language impairment, with an initial impression of primary progressive aphasia. Over time he developed progressive cerebellar ataxia and akinetic parkinsonism. There was a family history of ataxia in multiple family members. Levodopa was prescribed up to 450 mg per day without benefit. Genetic testing at age 69 revealed a heterozygous F198S mutation in the PRNP gene, with MV heterozygosity at codon 129. At age 70, he developed mild generalized choreiform dyskinesia. Levodopa was discontinued, resulting in the resolution of dyskinesia with a concomitant marked worsening of akinetic parkinsonism. DaT-SPECT demonstrated bilaterally reduced putaminal binding. This case highlights that GSS can resemble atypical parkinsonism both clinically and with DaT-SPECT imaging. Taking a salient family history and other clinical features into consideration, GSS should be added to the differential diagnoses of such patients.
RESUMEN
Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the Fmr1 knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in Fmr1 KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the Fmr1 KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy.
