<p>Table 1. Age of onset, sex, duration of illness and clinical features of 38 European FFI cases Case ID Age of Sex Duration of Presenting clinical features Other investigations Source onset illness (months) S-01 38 F 10 Anxiety (1), nervousness (1), tremor, dysarthria, ataxia, Not performed Case 6/III-12 [1] memory loss S-02 69 F 18 Ataxia (1), dysarthria, dysmetria, dysphagia Not performed Case 6/II-7 [1]</p><p>S-03 54 M 15 Ataxia (1), dysarthria, myoclonus, pyramidal signs, Thalamo-olivary degeneration, mild cortical spongiosis Case 10/III-2 [1] hallucinations, dementia CSF 14-3-3: negative negative IHC PrPres detection S-04 76 F 8 Insomnia (1), dysarthria, dyaphoresis, inattention, Thalamo-olivary and cerebellar degeneration Case 6/II-5 [1] disorientation, gait ataxia, dementia S-05 43 F 12 Depression (1), apathy (1), anxiety (1), weight loss, Thalamo-olivary degeneration, mild cerebellar changes, negative Case 6/III-9 [1] hyperthermia, diaphoresis, tremor dysarthria, ataxia, IHC PrPres detection myoclonus S-06 56 F 20 Blurred vision (1), anxiety, dysarthria, dysphagia, Olivo-cerebellar degeneration Case 11/III-1 [1] tremor, diplopia, dysmetria, ataxia, memory loss S-07 F NP Asymptomatic carrier</p><p>S-08 54 M 14 Blurred vision (1), diplopia (1), nystagmus, ocular PET/SPECT: thalamic hypoperfusion Case 4/III-6 [1] flutter, insomnia, ataxia, dysarthria, dementia CSF 14-3-3: negative Thalamo-olivary degeneration negative IHC PrPres detection S-09 62 M 14 Apraxia (1), loss of verbal fluency, agraphia, imitation PET/SPECT: frontal hypoperfusion Case 4/III-5 [1] behaviour, dementia CSF 14-3-3: positive (haematic CSF) Diffuse spongiform degeneration Positive IHC PrPres detection S-10 59 F 12 Anxiety (1), diurnal hypersomnia, nocturnal insomnia, PET/SPECT: thalamic hypometabolism Case 7/IV-5 [1] inattention, tremor, myoclonus, dementia CSF 14-3-3: negative Thalamo-olivary degeneration Positive IHC PrPres detection S-11 M NP Asymptomatic carrier</p><p>S-12 58 M 8 Memory loss (1), insomnia, diaphoresis, tremor, PET/SPECT: Thalamic hypoperfusion Case 12/III-1 [1] myoclonus, dementia CSF 14-3-3: negative Thalamic, olivary and cerebellar degeneration Negative IHC PrPres detection S-13 50 M 19 Ataxia (1), abnormal ocular movements, dysarthria, Not performed Case 5/III-2 [1] depression, insomnia, nocturnal agitation, weight loss, diaphoresis, dementia S-14 58 M 40 Ataxia (1), arterial hypertension, tachycardia, irregular Not performed Case 5/III-1 [1] respiration, dementia Case ID Age of Sex Duration of Presenting clinical features Other investigations Source onset illness (months) S-15 38 M 5 Parkinsonism (1), dementia, myoclonus, sleep CSF 14-3-3: negative Data from the authors disturbances (insomnia), dysautonomia EEG: abnormal slow rhythms but no PSWC Confirmed at autopsy (FFI) MRI: normal S-16 46 F 13 Depression (1), dementia, dysautonomia, insomnia, No autopsy Data from the authors dystonia parkinsonism EEG : abnormal slow rhythms but no PSWC PSG:+ MRI: normal S-17 47 M 18 Sleep disturbances (insomnia) (1), ataxia, dementia, No autopsy Data from the authors parkinsonism PSG + S-18 55 F ? Sleep disturbances (insomnia) (1) No autopsy Data from the authors PSG + S-19 49 F 3 Ataxia (1), dementia, myoclonus, abnormal ocular Confirmed at autopsy (FFI) Data from the authors movements EEG: abnormal abnormal slow rhythms, but no PSWC PSG + MRI: normal S-20 83.4 F 14.10 Rapidly progressive dementia (1), ataxia Negative 14-3-3 test Data from the authors</p><p>S-21 70.6 F 9.10 Rapidly progressive dementia (1), neuropsychiatric Not performed Data from the authors symptoms NP, not presenting; (1) denotes the first clinical symptoms observed</p><p>Sources</p><p>1. Zarranz JJ, Digon A, Atares B, Rodriguez-Martinez AB, Arce A, Carrera N, Fernandez-Manchola I, Fernandez-Martinez M, Fernandez-Maiztegui C, Forcadas I, Galdos L, Gomez-Esteban JC, Ibanez A, Lezcano E, Lopez dM, Marti-Masso JF, Mendibe MM, Urtasun M, Uterga JM, Saracibar N, Velasco F, de Pancorbo MM (2005) Phenotypic variability in familial prion diseases due to the D178N mutation. J Neurol Neurosurg Psychiatry 76:1491-1496</p><p>2. Cortelli P, Perani D, Parchi P, Grassi F, Montagna P, De Martin M, Castellani R, Tinuper P, Gambetti P, Lugaresi E, Fazio F (1997) Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistant prion protein. Neurology 49:126-133</p><p>3. Cortelli P, Gambetti P, Montagna P, Lugaresi E (1999) Fatal familial insomnia: clinical features and molecular genetics. J Sleep Res 8 Suppl 1:23-29</p><p>4. Manetto V, Medori R, Cortelli P, Montagna P, Tinuper P, Baruzzi A, Rancurel G, Hauw JJ, Vanderhaeghen JJ, Mailleux P (1992) Fatal familial insomnia: clinical and pathologic study of five new cases. Neurology 42:312-319</p><p>5. Medori R, Montagna P, Tritschler HJ, LeBlanc A, Cortelli P, Tinuper P, Lugaresi E, Gambetti P (1992) Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178. Neurology 42:669-670</p>