title: A proposal of new diagnostic pathway for fatal familial insomnia.
abstract: BACKGROUND
  In absence of a positive family history, the diagnosis of fatal familial insomnia (FFI) might be difficult because of atypical clinical features and low sensitivity of diagnostic tests. FFI patients usually do not fulfil the established classification criteria for Creutzfeldt-Jakob disease (CJD); therefore, a prion disease is not always suspected.
  
  
  OBJECTIVE
  To propose an update of diagnostic pathway for the identification of patients for the analysis of D178-M129 mutation.
  
  
  METHODS
  Data on 41 German FFI patients were analysed. Clinical symptoms and signs, MRI, PET, SPECT, polysomnography, EEG and cerebrospinal fluid biomarkers were studied.
  
  
  RESULTS
  An algorithm was developed which correctly identified at least 81% of patients with the FFI diagnosis during early disease stages. It is based on the detection of organic sleep disturbances, either verified clinically or by a polysomnography, and a combination of vegetative and focal neurological signs and symptoms. Specificity of the approach was tested on three cohorts of patients (MM1 sporadic CJD patients, non-selected sporadic CJD and other neurodegenerative diseases).
  
  
  CONCLUSIONS
  The proposed scheme may help to improve the clinical diagnosis of FFI. As the sensitivity of all diagnostic tests investigated but polysomnography is low in FFI, detailed clinical investigation is of special importance.
authors.affiliation: Clinical Dementia Center and National Reference Center for TSE at Department of Neurology Georg-August University, , Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Krasnianski
authors.forename: P
authors.initials: P
authors.lastname: Sanchez Juan
authors.forename: Claudia
authors.initials: C
authors.lastname: Ponto
authors.forename: M
authors.initials: M
authors.lastname: Bartl
authors.forename: U
authors.initials: U
authors.lastname: Heinemann
authors.forename: D
authors.initials: D
authors.lastname: Varges
authors.forename: W J
authors.initials: WJ
authors.lastname: Schulz-Schaeffer
authors.forename: H A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: I
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis; D019091:Critical Pathways / Q000592:standards / Q000639:trends; D003937:Diagnosis, Differential; D004569:Electroencephalography; D005260:Female; D005858:Germany; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000175:diagnosis* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017286:Polysomnography; D011159:Population Surveillance / Q000379:methods; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D017096:Prion Diseases / Q000175:diagnosis; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions
keywords: CREUTZFELDT-JAKOB DISEASE; DEMENTIA