Ant pyramidal indicators had been observed. Impairment of cerebellar function and multifocal cognitive loss was noticed by neurologic examination. Behavioral abnormalities with delusions, visual hallucinations, confabulations, mental confusion were evident in the following days. These symptoms had been scarcely responsive to Quetiapine but were partially controlled by the use of Haloperidol. Neuropsychological assessment showed behavioral disturbances with depression and visual hallucinations, moderate-to-severe cognitive dysfunctions, primarily consisting of impairment of thought content and semantic fluency, poor orientation in time and spot, memory deficits, confabulation, dyspraxia. Laboratory evaluation revealed improve of FT4 (9.9 ng/ dL, n.v. 0,70-1,48) and low TSH levels (0.13 UI/mL, n.v. 0,45-3,50). The imbalance of thyroid function was corrected by the adjustment of pharmacologic therapy for hyperthyroidism with transient optimistic effects on psychic disturbances (regression of delusions/hallucinations and improvement of mental confusion). CSF TSTA3 Protein E. coli analysis showed absence of 14-3 protein. CSF levels of total tau protein had been 392 pg/ml (n.v. 500 pg/ml). EEG showed a diffuse slowing from the background activitytowards the delta rhythm. An improvement on the EEG profile was observed after neuroleptic therapy and correction of thyroid dysfunction. Brain MRI showed multiple little ischemic foci in white matter of both brain hemispheres, and diffuse cortical atrophy involving primarily left frontal and temporal lobi (Fig. 3, panels b,e). All these clinical investigations had been performed 2 years right after the illness onset. On account of the prominence of behavioral adjustments in her clinical picture and to brain MRI findings, the patient was initially diagnosed as frontotemporal dementia (FTD). Over the following months, the clinical picture evolved towards tetraparesis, serious ataxia, and additional cognitive deterioration. When the family history of the patient emerged along with the presence of a PRNP mutation was confirmed in her sister (Case 1), the evaluation of PRNP gene was carried out also in this patient and revealed the presence in the Valine-to-Isoleucine substitution at codon 189 with Methionine/Valine polymorphism at codon 129. The patient died nine months immediately after hospital discharge, about 33 months immediately after the onset in the disease. No autopsy was performed. Nevertheless, RT-QuIC analysis of CSF sample collected in vitam was carried out and was good, confirming the presence of pathological prion protein. Taking into account her clinical findings, Case 2 met the WHO 1998 criteria or the updated criteria by Zerr et al. [51] for `possible’ sCJD, as she had no positive ancillary tests. Nevertheless, the outcomes of the RT-QuIC test on CSF, made reasonable a diagnosis of `probable’ CJD based on the proposed new criteria from the UK and Germany that allow any neurological syndrome having a positive RT-QuIC.Di Fede et al. Acta Neuropathologica Communications(2019) 7:Web page 7 EphA4 Protein MedChemExpress ofCaseThis patient was a 71-year-old man using a 2-month history of short-term memory deficits and fluctuating confusion (Table 1). The family members history was unremarkable except for two cases of late-onset depression ( 60 years) in two sisters of his father. The patient underwent neurologic evaluation that resulted to become regular: a presumptive diagnosis of reactive depression was made as well as a therapy with sertraline was suggested. Since the lack of response and the worsening of cognitive symptoms, the patient was subje.