Neurological Sciences | 2021
Early and long-term cognitive features in sporadic Creutzfeldt-Jakob disease
Abstract
To the Editor-in-Chief, Creutzfeldt-Jakob disease (CJD), caused by misfolding of prion protein (PrP), is characterized by subacute dementia, myoclonus, dystonia, postural changes, ataxia, and akinetic mutism. The sporadic form (sCJD), the most common, frequently begins in the seventh decade of life and has an average course of 4 months associated with the polymorphism methionine/valine (MM1/MV1, VV1, VV2, MV2, MM2-thalamic, or MM2-cortical) of the codon 129 of the prion protein gene (PRNP) [1]. Here we describe a right-handed patient (FE) with progressive smell loss, insomnia, and depression started at 57 years. At 59 years, FE showed writing and naming failures and reduced ability to handle stressful situations, which affected work activities. Magnetic resonance (MRI) revealed hyperintensities and reduced diffusivity in the occipital, parietal, and insular cortex bilaterally and normal temporal lobe structures. Electroencephalogram (EEG) showed an unorganized electric activity with prominent anterior alpha rhythm and theta waves on the left hemisphere. The Mini Mental State Examination (MMSE) score was 26/30. The olfactory mucous Real-Time Quaking-Induced Conversion (RT-QuIC) detected the presence of PRNP, while the cerebrospinal fluid (CSF) examination showed a weak 14.3.3 protein positivity. The genetic study revealed heterozygous methionine/valine (MV) polymorphism and no mutations. Upon admission to hospital, at age 61, FE reported a progressive speech loss and neurological examination showed nonfluent aphasia, ideomotor apraxia, and apathy associated with preserved disease awareness and motor functions. The neuropsychological assessment with tests previously adopted in CJD [2] showed a moderate cognitive decline (MMSE score 19.49/30) and an impairment of selective attention, working memory, planning, task control, sensitivity to conflicting information, ideomotor and orofacial praxia, and visuospatial long-term memory. Episodic memory and supraspan verbal learning were normal. An impairment of verbal fluency with phonemic or semantic cues and of object naming, as well as an inappropriate comprehension of very long sentences, were main language features. Likewise, at the Aphasia Neuropsychological Examination (ENPA), the generation of names on semantic (animal, object) or phonemic (F, A, S) cues and of verbs revealed the most severe alterations along with the written naming of figures and verbs. In addition, the ENPA revealed an impairment of the transcoding and reading of nonwords (lexicalization errors, omissions), transcoding and writing of words and nonwords (altered phoneme-grapheme association, reduced access to the lexical store, errors in the conversion of homophone words, morphological mistakes, neologisms), and conversion of words into Arabic numbers (errors in lexicalization, class selection, digit location and syntax); the repetition of words or nonwords, reading aloud words and phrases, words and color naming, and the comprehension of words and active or passive short sentences were well preserved. MRI put in evidence marked hyperintensities in the insula, temporal, occipital, and parietal cortex and orbitofrontal gyri, prevalent on the left hemisphere (Fig. 1A). The visual evoked potentials (EP) were normal. The analyses of the CSF and PRNP revealed the 14.3.3 protein, a normal TAU protein level, and a MV polymorphism. Six months later, neurological examination revealed adequate disease awareness and autobiographical memory and a worsening of aphasia, with severe alterations of syntax, comprehension, naming, and inhibitory control. Clinical assessment also revealed the presence of utilization gestures, orofacial, ideomotor and constructive apraxia, impairment of spatial exploration and perception, body schema and visuomotor coordination, mild ataxia, and arms weakness, without involuntary movements. In comparison with previous examination, MRI revealed additional hyperintensities in the * A. R. Giovagnoli [email protected]