Fatal Familial Insomnia

Abstract

To our knowledge, this is the first report of FFI in a family of Chinese descent. This supports the worldwide distribution of FFI, and despite differences in genetic background, the clinical and pathological findings are similar to those found in white patients with FFI.

Case of fatal familial insomnia caused by a d178n mutation with phenotypic similarity to Hashimoto’s encephalopathy

“…The role of corticosteroids in prion disease is currently under investigation with previous studies12 suggesting that corticosteroids might play a role in the pathogenesis of neurodegenerative disorders in general. The discrepancy between our patient having initial symptomatic improvement with corticosteroids and the CJD patient reported by Jang et al , with severe deterioration, could be due to pathophysiological differences between CJD and FFI 1 13–17. A weakness of this case is the absence of polysomnography data as Wu et al have reported abnormalities in sleep architecture and REM sleep intrusion in wakefulness in five Chinese patients with FFI 18…”

Case of fatal familial insomnia caused by a d178n mutation with phenotypic similarity to Hashimoto’s encephalopathy

“…The role of corticosteroids in prion disease is currently under investigation with previous studies12 suggesting that corticosteroids might play a role in the pathogenesis of neurodegenerative disorders in general. The discrepancy between our patient having initial symptomatic improvement with corticosteroids and the CJD patient reported by Jang et al , with severe deterioration, could be due to pathophysiological differences between CJD and FFI 1 13–17. A weakness of this case is the absence of polysomnography data as Wu et al have reported abnormalities in sleep architecture and REM sleep intrusion in wakefulness in five Chinese patients with FFI 18…”

Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N-homozygous 129M genotype

“…Within 6 acquired brain autopsy, 1 neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; the remaining 5, the histopathology was typical of FFI. Harder et al,1999 [ 9 ] German 7 patients with D178N, including 5 patients with 129M/M,2 patients with 129M/V 7 genetic diagnosis of FFI, but clinical diagnosis with CJD, FFI, AD, GSS,etc Taniwaki et al,2000 [ 10 ] A Japanese family 3 patients with D178N-129M 3 patients with cerebral ataxia without overt insomnia diagnosed fCJD Dauvilliers et al,2004 [ 22 ] French 1 patient with D178N-129M/M FFI presented with circadian rhythms changes Spacey et al,2004 [ 23 ] A family of Chinese descent 1 patient with D178N-129M/M, 1 patietn genotype unclear 2 patients from this kindred were FFI Zarranz et al,2005 [ 12 ] Spanish (Basque born families) 17 patients carrying D178N-129M 7 out of 17 patients has CJD phenotype Synofzik et al,2009 [ 17 ] A German family all with D178N but 129 codon was not all clear demonstrated 1GSS with D178N-M129V, 2 CJD, 1 FFI, 1 atypical Alzheimer, 1 Freidreich ataxia, 1 brain degeneration, 1 brain softening, 1 asymptomatic member with D178N-129M Saitoh et al,2010 [ 24 ] Japanese 2 patients with D178N-129M/M 1 CJD(D178N-129M/M) phenotype and 1 FFI phenotype(D178N-129M/M) with the same PrP sc ratio glycoform Lin et al,2015 [ 7 ] Chinese 1 patient with D178N-129M 1 CJD phenotype Megelin et al,2017 [ 25 ] A French family …”

Midbrain Hypometabolism in Fatal Familial Insomnia: A Case Report and a Statistical Parametric Mapping Analysis of a Korean Family

“…Interestingly, all of the suspected and confirmed FFI patients in this family were male, while the obligate female carriers did not present FFI-related signs or symptoms. So far, no specific sex dominance has been reported in previous studies of FFI kindred from different races and regions [ 1 , 3 , 4 , 5 , 6 , 7 ]. Our present case suggests that the penetrance of FFI could be sex-selective, at least in a specific kindred.…”

Case of fatal familial insomnia caused by a d178n mutation with phenotypic similarity to Hashimoto’s encephalopathy

“…The role of corticosteroids in prion disease is currently under investigation with previous studies12 suggesting that corticosteroids might play a role in the pathogenesis of neurodegenerative disorders in general. The discrepancy between our patient having initial symptomatic improvement with corticosteroids and the CJD patient reported by Jang et al , with severe deterioration, could be due to pathophysiological differences between CJD and FFI 1 13–17. A weakness of this case is the absence of polysomnography data as Wu et al have reported abnormalities in sleep architecture and REM sleep intrusion in wakefulness in five Chinese patients with FFI 18…”

Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N-homozygous 129M genotype

“…Within 6 acquired brain autopsy, 1 neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; the remaining 5, the histopathology was typical of FFI. Harder et al,1999 [ 9 ] German 7 patients with D178N, including 5 patients with 129M/M,2 patients with 129M/V 7 genetic diagnosis of FFI, but clinical diagnosis with CJD, FFI, AD, GSS,etc Taniwaki et al,2000 [ 10 ] A Japanese family 3 patients with D178N-129M 3 patients with cerebral ataxia without overt insomnia diagnosed fCJD Dauvilliers et al,2004 [ 22 ] French 1 patient with D178N-129M/M FFI presented with circadian rhythms changes Spacey et al,2004 [ 23 ] A family of Chinese descent 1 patient with D178N-129M/M, 1 patietn genotype unclear 2 patients from this kindred were FFI Zarranz et al,2005 [ 12 ] Spanish (Basque born families) 17 patients carrying D178N-129M 7 out of 17 patients has CJD phenotype Synofzik et al,2009 [ 17 ] A German family all with D178N but 129 codon was not all clear demonstrated 1GSS with D178N-M129V, 2 CJD, 1 FFI, 1 atypical Alzheimer, 1 Freidreich ataxia, 1 brain degeneration, 1 brain softening, 1 asymptomatic member with D178N-129M Saitoh et al,2010 [ 24 ] Japanese 2 patients with D178N-129M/M 1 CJD(D178N-129M/M) phenotype and 1 FFI phenotype(D178N-129M/M) with the same PrP sc ratio glycoform Lin et al,2015 [ 7 ] Chinese 1 patient with D178N-129M 1 CJD phenotype Megelin et al,2017 [ 25 ] A French family …”

Midbrain Hypometabolism in Fatal Familial Insomnia: A Case Report and a Statistical Parametric Mapping Analysis of a Korean Family

“…Interestingly, all of the suspected and confirmed FFI patients in this family were male, while the obligate female carriers did not present FFI-related signs or symptoms. So far, no specific sex dominance has been reported in previous studies of FFI kindred from different races and regions [ 1 , 3 , 4 , 5 , 6 , 7 ]. Our present case suggests that the penetrance of FFI could be sex-selective, at least in a specific kindred.…”

Case of fatal familial insomnia caused by a d178n mutation with phenotypic similarity to Hashimoto’s encephalopathy

“…The role of corticosteroids in prion disease is currently under investigation with previous studies12 suggesting that corticosteroids might play a role in the pathogenesis of neurodegenerative disorders in general. The discrepancy between our patient having initial symptomatic improvement with corticosteroids and the CJD patient reported by Jang et al , with severe deterioration, could be due to pathophysiological differences between CJD and FFI 1 13–17. A weakness of this case is the absence of polysomnography data as Wu et al have reported abnormalities in sleep architecture and REM sleep intrusion in wakefulness in five Chinese patients with FFI 18…”

Corticobasal manifestations of Creutzfeldt-Jakob disease with D178N-homozygous 129M genotype

“…Within 6 acquired brain autopsy, 1 neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; the remaining 5, the histopathology was typical of FFI. Harder et al,1999 [ 9 ] German 7 patients with D178N, including 5 patients with 129M/M,2 patients with 129M/V 7 genetic diagnosis of FFI, but clinical diagnosis with CJD, FFI, AD, GSS,etc Taniwaki et al,2000 [ 10 ] A Japanese family 3 patients with D178N-129M 3 patients with cerebral ataxia without overt insomnia diagnosed fCJD Dauvilliers et al,2004 [ 22 ] French 1 patient with D178N-129M/M FFI presented with circadian rhythms changes Spacey et al,2004 [ 23 ] A family of Chinese descent 1 patient with D178N-129M/M, 1 patietn genotype unclear 2 patients from this kindred were FFI Zarranz et al,2005 [ 12 ] Spanish (Basque born families) 17 patients carrying D178N-129M 7 out of 17 patients has CJD phenotype Synofzik et al,2009 [ 17 ] A German family all with D178N but 129 codon was not all clear demonstrated 1GSS with D178N-M129V, 2 CJD, 1 FFI, 1 atypical Alzheimer, 1 Freidreich ataxia, 1 brain degeneration, 1 brain softening, 1 asymptomatic member with D178N-129M Saitoh et al,2010 [ 24 ] Japanese 2 patients with D178N-129M/M 1 CJD(D178N-129M/M) phenotype and 1 FFI phenotype(D178N-129M/M) with the same PrP sc ratio glycoform Lin et al,2015 [ 7 ] Chinese 1 patient with D178N-129M 1 CJD phenotype Megelin et al,2017 [ 25 ] A French family …”

Midbrain Hypometabolism in Fatal Familial Insomnia: A Case Report and a Statistical Parametric Mapping Analysis of a Korean Family

“…Interestingly, all of the suspected and confirmed FFI patients in this family were male, while the obligate female carriers did not present FFI-related signs or symptoms. So far, no specific sex dominance has been reported in previous studies of FFI kindred from different races and regions [ 1 , 3 , 4 , 5 , 6 , 7 ]. Our present case suggests that the penetrance of FFI could be sex-selective, at least in a specific kindred.…”