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Objective To investigate the clinical features,polysomnography,imaging examination,genetic analysis and laboratory examination of eight patients with familial fatal insomnia (FFI).Methods The clinical data,neuropsychological examination,results of cerebrospinal fluid analysis,imaging examination and polysomnography of eight patients with FFI in Xuanwu Hospital,Capital Medical University from 2009 to 2018 were retrospectively analyzed and summarized.Results Among the eight FFI patients,there were 3 males and 5 females,the onset age being (49.8+14.3) years (19 to 64 years) and the course of disease being eight to 18 months.D178N mutation in the PRNP gene of chromosome 20 and 129 amino acid polymorphisms of M/M were found in genetic examination in all the eight patients,of which five patients had family history.All the patients had sleep disorders,sleep-related involuntary movement,sleep-related dyspnea,laryngeal stridor.All the patients showed rapid progressive dementia with or without symptoms or signs of psychosis,ataxia,pyramidal and extrapyramidal.All the eight patients had progressive sympathetic symptoms,including hypertension,sweating,tachycardia,irregular breathing,and dysarthria.Cerebrospinal fluid 14-3-3 protein was found positive in one patient,and negative in seven patients.Electroencephalograph showed diffuse slow wave and non periodic synchronous discharge.Single-photon emission computed tomography or 18F fluorodeoxyglucose positron emission tomography showed decreased thalamic glucose metabolism in three patients.Seven patients showed decreased total sleep time,sleep awakening cycle disorder,especially the reduction or loss of rapid eye movement,laryngeal stridor and involuntary movement in polysomnography.Conclusions FFI is characterized by sleep disorder,sleep-related involuntary movement,dyspnea,laryngosis,rapid progressive dementia and sympathetic symptoms.The family history,polysomnography and positron emission tomography are helpful for the diagnosis of FFI.PRNP gene detection can confirm the diagnosis of FFI.
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Objective To explore the clinical,imaging,genetic features in a case of fatal familial insomnia (FFI),and review related literatures.Methods A case of middle-aged woman diagnosed as frontotemporal dementia based on the preliminary manifestation of abnormal mental behavior was reported.The clinical features,imaging characteristics,electroencephalogram and polysomnogram of the patient were analyzed,and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP).Results This patient was a middle-aged woman,whose clinical manifestations were abnormal mental behavior,rapid progressive dementia and intractable insomnia,abnormal night sleep behavior and laryngeal stridor.Brain MRI indicated frontotemporal lobe atrophy.Non-sleep disturbance was observed in polysomnography.The cerebrospinal fluid was negative for 14-3-3 protein.The results of PRNP sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions Detection of PRNP plays an important role in the diagnosis of FFI.Patients suspected of FFI in clinic should be detected for genetic testing.Whether the frontotemporal lobe atrophy was caused by FFI or concurrent with FFI remains to be further verified.
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ObjectiveTo explore clinical,histopathological and genetic features in a case of fatal familial insomnia (FFI) and related literatures were reviewed. Methods The clinical features in one patient with FFI were analyzed,and the dead patient was examined at autopsy and histopathological studies were performed on the brain tissues; and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP). Results The main clinical features included intractable insomnia,psychiatric symptoms and abnormal night sleep behavior,unsteady gait,difficulty swallowing,sudden death,and positive family history. The pathological studies showed multiple neuronal loss and gliosis of brain tissues from the proband,predominated in thalamus; and analysis of PRNP revealed gene D178N mutation,and linkage with 129 methionine (Met) allele in the proband and a relative.ConclusionsFFI patients may manifest as sudden death,and may have prominent psychiatric symptoms; the corresponding gene mutation could occur in the asymptomatic carriers; the data of autopsy and brain tissue pathology is helpful for further understanding of this disease.
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Objective To investigate the characteristics of regional cerebral glucose metabolism in patients with fatal familial insomnia(FFI) using 18F-fluorodeoxyglucose(18F-FDG) PET. Methods Patient 1 with symptoms for 2 months and patient 2 with symptoms for 6 months were studied by brain 18 F-FDG PET.Compared with 20 normal controls, the data were analyzed by visual analysis at first, and then each patient was compared with age-matched normal controls using statistical parametric mapping( SPM ). Results As compared with 10 normal controls, metabolic changes in patient 1 was characterized by hypometabolism in thalamus, parietal cortices, caudate nucleus, pre-frontal cortices and posterior cingulate gyrus ( t ＞ 2. 82,P ＜0. 01 ). In patient 2, these changes were more obvious (t ＞ 2. 82, P ＜ 0. 01 ) with metabolic decrease also shown in temporal and occipital cortices ( t ＞ 2. 82, P ＜ 0. 01 ). Conclusion In FFI patients, brain metabolism changes are mainly manifested as hypometabolism in thalamus and cerebral cortex. The metabolic changes in cerebral cortex will be more widely spread with the development of FFI. 18F-FDG PET imaging was a valuable method to evaluate patients with FFI.