Unusual presentations in patients with E200K familial Creutzfeldt−Jakob disease

Abstract

Background and propose Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances, however some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this manuscript is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. Methods The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical MRI, electroencephalographic findings, elevated CSF tau protein levels, and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. Results The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ±7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However six patients had an unusual presentation including auditory agnosia, monoparesis, stroke like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. Discussion Our case series illustrate the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies.

E200k Familial Creutzfeldt-Jakob Disease Presenting with Subacute Multiple Cranial Neuropathy

“…The wide phenotypic variability of fCJD clinical onset has been previously reported by Chapman et al [3] and Cohen et al [1]. The risk of misdiagnosis and useless treatments comes down to unusual atypical presentations, particularly during the earliest stages of the disease.…”

“…Several unusual presentations in patients with E200K familial Creutzfeldt-Jakob Disease (fCJD) have been described in a recent review written by Cohen et al [1]. Herein, we report the case of a histologically confirmed E200K fCJD presenting with a subacute multiple cranial neuropathy.…”

“…In one paper [5], electrophysiologic examinations confirmed peripheral nervous system damage in patients with sporadic CJD and revealed also preclinical peripheral nervous system impairment. Furthermore, in another report [1] neuronal loss, gliosis and Prionic Protein (PrP) deposits were observed in the vestibular and cochlear nuclei of a patients presenting with sesnorineural hearing loss. Similarly, cranial nerves involvement in our patient could be explained by the direct deposition of PrP in oculomotor, VII, IX and X brainstem cranial nerves nuclei.…”

The insomnia phenotype in genetic Creutzfeldt–Jakob disease based on the E200K mutation

“…They are also typically accompanied by specific changes in EEG and brain MRI. Apart from these typical features, some patients present with unusual symptoms, such as a stroke-like presentation, alien hand syndrome, visual disturbances [5], spastic paraparesis [6] and others. Specific phenotypes and unusual symptoms could overlap in different PRNP mutations, or the same PRNP mutation could differ in phenotype: the D178N mutation could present as gCJD or FFI, determined by the type of codon 129 polymorphism; or the D178N-129M haplotype, expressing the FFI phenotype, corresponds to MM2-Thalamic (MM 2T or sporadic FI) in sporadic CJD (sCJD) [7].…”

Advances and insights into neurological practice 2016−17

“…The neurodegenerative diseases constitute major economic and social as well as medical challenges . The association of dementia with income, mortality, morbidity and medication use has been highlighted with a study from Denmark , with effects seen years before diagnosis.…”