Ribbon Sign Research Articles

P.355: Cortical ribbon sign in a liver transplant recipient with hepatic encephalopathy.

P.355: Cortical ribbon sign in a liver transplant recipient with hepatic encephalopathy.

Spontaneous calcified cerebral emboli: a comprehensive review and proposed diagnostic criteria.

Spontaneous calcified cerebral emboli (SCCE) secondary to aortic valve calcification are a rare and underreported cause of acute ischaemic stroke. Only five cases of SCCE secondary to bicuspid aortic valve calcification have been reported in the literature. This review includes a unique case example of acute ischaemic stroke secondary to SCCE, as the first manifestation of a calcified bicuspid aortic valve. This is the first clinical case of calcified cerebral emboli (CCE) associated with borderzone infarction ('cortical ribbon sign'). Whilst previously assumed that most CCE are secondary to iatrogenic causes, recent literature suggests the majority of CCE are spontaneous and clinically silent. Despite CT imaging widely considered the 'gold standard' for diagnosis, CCE are frequently misdiagnosed and missed entirely. Misdiagnosis of CCE may have catastrophic consequences due to the high risk of recurrence and missed opportunity to prevent neurological disability and death. This review presents a revised CCE diagnostic criteria, using evidence that has emerged over the last decade to create both Compulsory (Major) and Supporting (Minor) criteria. Current CCE management is not evidence based and remains largely speculative. SCCE may be the first manifestation of cardiac or vascular disease and diagnosis should trigger aggressive treatment of emboligenic sources. Future epidemiological studies, analysing symptomatic and asymptomatic SCCE patients, would be beneficial in providing accurate quantification of disease burden. Other future research directions include exploring intracranial stenting for CCE revascularisation and cerebral intravascular lithotripsy.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas

INTRODUCTION: Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Recognition of an intramedullary subependymoma on preoperative imaging can assist in operative planning and factor into the decision-making for gross- or sub-total resection. However, no definitive pathognomonic features have been reported on magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The “ribbon sign” was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. RESULTS: MRIs from 151 patients were reviewed, including 42 (28%) astrocytomas, 82 (54%) ependymomas, 8 (5.3%) gangliogliomas, and 19 (13%) hemangioblastomas. Of the 82 ependymomas, ten patients (12%) presented with intramedullary subependymomas. The ribbon sign was demonstrated on nine (90%) patients with histologically proven subependymomas. No other tumor types displayed the ribbon sign. CONCLUSIONS: The ribbon sign is a distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumor. Recognition of the sign should prompt clinicians to consider a diagnosis of subependymoma. Unlike their intracranial counterparts, resection of these lesions can be technically difficult, particularly in cases with poor demarcation between cord and tumor. Therefore, the risks and benefits of gross- vs. sub-total resection should be carefully considered and discussed with patients.

CT-Based Intratumoral and Peritumoral Radiomics Nomograms for the Preoperative Prediction of Spread Through Air Spaces in Clinical Stage IA Non-small Cell Lung Cancer

The study aims to investigate the value of intratumoral and peritumoral radiomics and clinical-radiological features for predicting spread through air spaces (STAS) in patients with clinical stage IA non-small cell lung cancer (NSCLC). A total of 336 NSCLC patients from our hospital were randomly divided into the training cohort (n = 236) and the internal validation cohort (n = 100) at a ratio of 7:3, and 69 patients from the other two external hospitals were collected as the external validation cohort. Univariate and multivariate analyses were used to select clinical-radiological features and construct a clinical model. The GTV, PTV5, PTV10, PTV15, PTV20, GPTV5, GPTV10, GPTV15, and GPTV20 models were constructed based on intratumoral and peritumoral (5 mm, 10 mm, 15 mm, 20 mm) radiomics features. Additionally, the radscore of the optimal radiomics model and clinical-radiological predictors were used to construct a combined model and plot a nomogram. Lastly, the ROC curve and AUC value were used to evaluate the diagnostic performance of the model. Tumor density type (OR = 6.738) and distal ribbon sign (OR = 5.141) were independent risk factors for the occurrence of STAS. The GPTV10 model outperformed the other radiomics models, and its AUC values were 0.887, 0.876, and 0.868 in the three cohorts. The AUC values of the combined model constructed based on GPTV10 radscore and clinical-radiological predictors were 0.901, 0.875, and 0.878. DeLong test results revealed that the combined model was superior to the clinical model in the three cohorts. The nomogram based on GPTV10 radscore and clinical-radiological features exhibited high predictive efficiency for STAS status in NSCLC.

Cortical ribbon sign on neuroimaging in a patient with hepatic encephalopathy secondary to herbal medicine usage.

Cortical ribbon sign on neuroimaging in a patient with hepatic encephalopathy secondary to herbal medicine usage.

EP21.17: Prenatal diagnosis 22q11.2 deletion syndrome with cross ribbon sign

EP21.17: Prenatal diagnosis 22q11.2 deletion syndrome with cross ribbon sign

When vision loss is beyond cataract: a case of fatal neurodegenerative disease (P1-9.010)

<h3>Objective:</h3> NA <h3>Background:</h3> Creutzfeldt Jakob disease (CJD) is a rare and fatal neurodegenerative disorder of unclear etiology. Presentation include myoclonic jerks, visual disturbances, pyramidal/extrapyramidal signs and rapidly progressive cognitive decline. Visual symptoms are a common manifestation of CJD. Here we present a case of progressive vision loss initially attributed to cataract with eventual diagnosis of CJD. <h3>Design/Methods:</h3> Patient is a 75-year-old woman with history of osteoporosis, dyslipidemia, and arthritis presented to the emergency (ED) with bilateral vision loss and cognitive decline. Symptoms started 8 weeks prior presentation with progressive vision loss and difficulty recognizing color and shapes. She also had intermittent horizontal diplopia. Patient was initially evaluated by an ophthalmologist where vision loss was attributed to cataract and underwent bilateral cataract extraction with no improvement in vision. Vision loss worsened and she became unable to recognize familiar faces or identify objects, and had recurrent falls. She suffered visual hallucination, progressive abnormal body posturing, memory loss, dysphagia and severe dysarthria. On her exam she was noted to be mute, unable to follow commands, and had stimulus induced myoclonic jerks of limbs. CXR, urine analysis, urine and blood cultures, and urine drug screen were all unrevealing. Serum and CSF paraneoplastic panel were negative. EEG showed absence of the posterior dominant rhythm. Brain MRI demonstrated cortical ribbon sign and hyperintensities of basal ganglia (image 1). CSF Rt-Quic was indeterminate. Given the history, exam and MRI findings, she was diagnosed with Heidenhain variant of CJD and passed away shortly after transfer to inpatient hospice. <h3>Results:</h3> NA <h3>Conclusions:</h3> CJD can present with isolated visual symptoms that precede cognitive decline by weeks. Detailed history and careful exam are essential for early diagnosis as this will allow patients and their families to prepare for the expected disease course, consider goals of care, and possibly have palliative care if desired. <b>Disclosure:</b> Dr. Abusamra has nothing to disclose. Dr. Ali has nothing to disclose. Dr. Sudhakar has nothing to disclose.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas

Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Anticipating a subependymoma on preoperative imaging can inform surgical decision-making and improve patient counseling. Here, we present our experience recognizing IMSC subependymomas on preoperative magnetic resonance imaging (MRI) based on a distinctive characteristic termed the "ribbon sign." We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The "ribbon sign" was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. MRIs from 151 patients were reviewed, including 10 patients with IMSC subependymomas. The ribbon sign was demonstrated on 9 (90%) patients with histologically proven subependymomas. Other tumor types did not display the ribbon sign. The ribbon sign is a potentially distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumors. Recognition of the ribbon sign should prompt clinicians to consider a diagnosis of subependymoma, aiding the neurosurgeon in planning the surgical approach and adjusting the surgical outcome expectation. Consequently, the risks and benefits of gross-versus subtotal resection for palliative debulking should be carefully considered and discussed with patients.

Unraveling rare form of adult-onset NIID by characteristic brain MRI features: A single-center retrospective review.

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with high clinical heterogeneity. Previous studies indicated that the high-intensity signals in the corticomedullary junction on diffusion-weighted imaging (DWI) on brain MRI, known as the "ribbon sign," could serve as a strong diagnostic clue. Here we used the explorative approach to study the undiagnosed rate of adult-onset NIID in a single center in China via searching for the ribbon sign in picture archive and communication system (PACS) and report the clinical and radiological features of initially undiagnosed NIID patients. Consecutive brain MRI of 21,563 adult individuals (≥18 years) in the PACS database in 2019 from a tertiary hospital were reviewed. Of them, 4,130 were screened out using the keywords "leukoencephalopathy" and "white matter demyelination." Next, all 4,130 images were read by four neurologists. The images with the suspected ribbon sign were reanalyzed by two neuroradiologists. Those with the ribbon sign but without previously diagnosed NIID were invited for skin biopsy and/or genetic testing for diagnostic confirmation. The clinical features of all NIID patients were retrospectively reviewed. Five patients with high-intensity in the corticomedullary junction on DWI were enrolled. Three patients were previously diagnosed with NIID confirmed by genetic or pathological findings and presented with episodic encephalopathy or cognitive impairment. The other two patients were initially diagnosed with limb-girdle muscular dystrophy (LGMD) with rimmed vacuoles (RVs) and normal pressure hydrocephalus (NPH) in one each. Genetic analysis demonstrated GGC repeat expansion in the NOTCH2NLC gene of both, and skin biopsy of the first patient showed the presence of intranuclear hyaline inclusion bodies. Thus, five of the 21,563 adult patients (≥18 years) were diagnosed with NIID. The distinctive subcortical high-intensity signal on DWI was distributed extensively throughout the lobes, corpus callosum, basal ganglia, and brainstem. In addition, T2-weighted imaging revealed white matter hyperintensity of Fazekas grade 2 or 3, atrophy, and ventricular dilation. Distinctive DWI hyperintensity in the junction between the gray and white matter can help identify atypical NIID cases. Our findings highly suggest that neurologists and radiologists should recognize the characteristic neuroimaging pattern of NIID.

Does Gadolinium Deposition Lead to Metabolite Alteration in the Dentate Nucleus? An MRS Study in Patients with MS.

Repeat contrast-enhanced MR imaging exposes patients with relapsing-remitting MS to frequent administration of gadolinium-based contrast agents. We aimed to investigate the potential metabolite and neurochemical alterations of visible gadolinium deposition on unenhanced T1WI in the dentate nucleus using MRS. This prospective study was conducted in a referral university hospital from January 2020 to July 2021. The inclusion criteria for case and control groups were as follows: 1) case: patients with relapsing-remitting MS, visible gadolinium deposition in the dentate nucleus (ribbon sign), >5 contrast-enhanced MR images obtained; 2) control 1: patients with relapsing-remitting MS without visible gadolinium deposition in the dentate nucleus, >5 contrast-enhanced MR images obtained; 3) control 2: patients with relapsing-remitting MS without visible gadolinium deposition in the dentate nucleus, <5 contrast-enhanced-MR images obtained; and 4) control 3: adult healthy individuals, with no contrast-enhanced MR imaging. Dentate nucleus and pontine single-voxel 12 × 12 × 12 MRS were analyzed using short TEs. Forty participants (10 per group; 27 [67.5%] female; mean age, 35.6 [SD, 9.6] years) were enrolled. We did not detect any significant alteration in the levels of NAA and choline between the studied groups. The mean concentrations of mIns were 2.7 (SD, 0.73) (case), 1.5 (SD, 0.8) (control 1), 2.4 (SD, 1.2) (control 2), and 1.7 (SD, 1.2) (control 3) (P = .04). The mean concentration of Cr and mIns (P = .04) and the relative metabolic concentration (dentate nucleus/pons) of lipid 1.3/Cr (P = .04) were significantly higher in the case-group than in healthy individuals (controls 1-3). Further analyses compared the case group with cumulative control 1 and 2 groups and showed a significant increase in lactate (P = .02), lactate/Cr (P = .04), and Cr (dentate nucleus/pons) (P = .03) in the case group. Although elevated concentrations of Cr, lactate, mIns, and lipid in the dentate nucleus of the case group indicate a metabolic disturbance, NAA and choline levels were normal, implying no definite neuronal damage.

Prediction model of early biomarkers of massive cerebral infarction caused by anterior circulation occlusion: Establishment and evaluation

ObjectiveThe purpose of this study is to establish and evaluate an early biomarker prediction model of massive cerebral infarction caused by anterior circulation occlusion.MethodsOne hundred thirty-four patients with acute cerebral infarction from January 2018 to October 2020 were selected to establish the development cohort for the internal test of the nomogram. Ninety-one patients with acute cerebral infarction hospitalized in our hospital from December 2020 to December 2021 were constituted the validation cohort for the external validation. All patients underwent baseline computed tomography (CT) scans within 12 h of onset and early imaging signs (hyperdense middle cerebral artery sign, obscuration of the lentiform nucleus, insular ribbon sign) of acute cerebral infarction were identified on CT by two neurologists. Based on follow-up CT images, patients were then divided into a massive cerebral infarction group and a non-massive cerebral infarction group. The nomogram model was constructed based on logistic regression analysis with R language. The nomogram was subsequently validated in an independent external validation cohort. Accuracy and discrimination of the prediction model were evaluated by a calibration chart, receiver operating characteristic (ROC) curve, and decision curve.ResultsThe indicators, including insular ribbon sign, reperfusion therapy, National Institutes of Health Stroke Scale (NHISS) score, previous cerebral infarction, and atrial fibrillation, were entered into the prediction model through binary logistic regression analysis. The prediction model showed good predictive ability. The area under the ROC curve of the prediction model was 0.848. The specificity, sensitivity, and Youden index were 0.864, 0.733, and 0.597, respectively. This nomogram to the validation cohort also showed good discrimination (AUC = 0.940, 95% CI 0.894–0.985) and calibration.ConclusionDemonstrating favorable predictive efficacy and reproducibility, this study successfully established a prediction model of CT imaging signs and clinical data as early biomarkers of massive cerebral infarction caused by anterior circulation occlusion.

Predictors of CT Morphologic Features to Identify Spread Through Air Spaces Preoperatively in Small-Sized Lung Adenocarcinoma

ObjectivesThis study aimed to explore the predictive CT features of spread through air spaces (STAS) in patients with small-sized lung adenocarcinoma.MethodsFrom January 2017 to May 2019, patients with confirmed pathology of small-sized lung adenocarcinoma (less than or equal to 2 cm) and who underwent surgery were retrospectively analyzed. The clinical, pathological, and surgical information and CT features were analyzed.ResultsA total of 47 patients with STAS (males, 61.7%; mean age, 56 ± 8years) and 143 patients without STAS (males, 58%; mean age, 53 ± 11 years) were included. Pathologically, papillary, micropapillary, solid predominant subtypes, and vascular and pleural invasion were most commonly observed features in the STAS group. Radiologically, higher consolidation tumor ratio (CTR), presence of spiculation, satellites, ground glass ribbon sign, pleural attachment, and unclear tumor–lung interface were more commonly observed features in the STAS group. CTR, presence of ground glass ribbons and pleural connection, and absence of cystic airspaces were considered as stable predictors of STAS in multivariate logistic models. The receiver operating characteristic curve (ROC) analysis for predicting STAS demonstrated higher area under the curve (AUC) in the model that used CTR (0.760, 95% confidence interval, 0.69–0.83) for predicting STAS than in the model that used long diameter of entire lesion (0.640).ConclusionsCTR is the best CT sign for predicting STAS in small-sized lung adenocarcinoma. The ground glass ribbon is a newly found indicator and has the potential for predicting STAS.

Evaluation of the Clinical, Laboratory, and Radiological Findings and Treatment of 19 Cases of Pancreatic Echinococcosis.

BackgroundHydatid disease is a severe health problem in endemic areas. In recent years, the incidence of this disease in China has been increasing. As the imaging characteristics of pancreatic echinococcosis (PE) are similar to those of cystic diseases, such as cysts, tuberculosis, and tumors, PE is often misdiagnosed and mistreated.MethodsThe clinical manifestations, laboratory tests, radiological findings, and treatment of 19 patients with PE between January 2006 and December 2018 in 2 hospitals were retrospectively analyzed.ResultsThe mean age of the patients was 38 years, and the ratio of women to men was 2. All patients came from rural areas. Clinical manifestations included cholestatic jaundice, mass, nausea, pain, and swelling. Hemagglutination inhibition test results were positive for all patients. Enzyme-linked immunosorbent assay test results were positive in 17 cases (89.5%). Foci in the pancreas were head in 52.6%, body in 26.3%, body and tail in 15.8%, tail in 5.3%. The size of lesions’ diameter ranged from 1 to 12 cm (mean, 6.5 cm). The imaging features of PE included the presence of (a) daughter cysts on abdominal computed tomography (CT) and/or magnetic resonance imaging (MRI); (b) internal cyst wall dissection and ribbon sign on abdominal CT and/or MRI; (c) typical eggshell cyst wall calcification on abdominal CT.ConclusionsFor patients with cystic lesions on CT and/or MRI combined with epidemiological history and positive echinococcosis serology, doctors can correctly diagnose PE earlier. Surgical treatment combined with drugs can reduce the mortality of PE, leading to a better prognosis.

A probable role of copper in the comorbidity in Wilson\u2019s and Creutzfeldt-Jakob\u2019s Diseases: a case report

BackgroundTo the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson’s and Creutzfeldt-Jakob disease (CJD), linked through copper.Case presentationA 44-year-old male with a history of inherited Wilson’s disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination. Laboratory tests, including liver enzymes, copper and serum ammonia were all within normal range. The brain MRI showed increased T2 signal in the caudate nuclei, attributed to copper deposition in the context of Wilson’s disease. In the electroencephalogram, periodic sharp discharges were eminent, initially unilateral and then generalized. The positive 14–3-3 protein in the cerebrospinal fluid (CSF) and the new brain MRI, that demonstrated elevated DWI signal not only in the basal ganglia but also in parts of the cerebral cortex (cortical ribbon sign), all supportive of a possible CJD diagnosis. The detection of PrPSc in the patient’s CSF, using the RT-QuIC method, which has a 99.4–100% specificity for CJD, made the diagnosis of CJD highly probable.ConclusionThis is the first report of Wilson’s and Creutzfeldt-Jakob diseases co-morbidity in the literature, which could evoke a possible role of copper in the pathogenesis of CJD.

Hyperdense middle cerebral artery sign

Not available.

Familial fatal insomnia: A Taiwanese case report

Familial fatal insomnia (FFI) is a rare autosomal dominant inherited prion disease, which is characterized by severe sleep disorder, dysautonomia, motor signs and abnormal behavior. It is caused by D178N mutation in the prion protein gene accompanied by the presence of a methionine at the codon 129 polymorphic site on the mutated allele. Herein we reported a 37-year-old man presenting with unintentional weight loss of 24 kgs and progressive cognitive decline with episode of visual hallucination in 6 months. On examination, he had speech disturbance, general muscle wasting with muscle strength of 4/5, involuntary jerks, tremor-like movements, and gait disturbance. The electroencephalography did not show characteristic periodic sharp wave complexes and there was no focal brain lesion or abnormal cortical ribbon sign on magnetic resonance imaging of brain. Once he scored 11/30 on the Mini-Mental State Examination (MMSE) but he became speechless and unresponsive to verbal command in 1 month. He soon developed dysphagia and stridor during sleep. He was died of pneumonia. We didn't have chance to perform polysomnography although sleep disturbance was mentioned by his family. The CSF was acellular and normal biochemistry except positive for 14–3-3 protein. Genetic analysis by the Taiwan Centers for Disease Control identified D178N and M129 V mutations of PRNP gene. Early diagnosis of FFI might be challenging in such case because of low sensitivity of diagnostic tests and absence of family history. Rapidly progressive dementia with drastic weight loss can be an important clinical clue and genetic analysis is required for diagnosis.

P65-F EEG evolution in a case of rapidly progressive dementia

Background Rapidly progressive dementia can be caused by several factors like neurodegenerative, toxic/metabolic, infectious, autoimmune or neoplastic disorders. Here I present a case of this type and the diagnostic process leading to diagnosis. Material and methods This case describes a woman in her sixties admitted to hospital with dementia and anxiety as initial symptoWithin 2 month progression of these symptoms and appearance of apraxia, visual affection and cerebellar gait. The diagnostic process is illustrated. including consecutive EEGs, PET, MRi, CSF markers. Results Initial MRi was considered normal and first EEG with normal posterior dominant rhythm and bi-fronto-temporal 2–3 Hz activity (leftsided dominance) and no paroxystic activity. Repeated tests revealed classic changes seen in sporadic CJD on MRi in the form of cortical ribbon sign and adynamic periodic paroxyms and low frequency activity (2–3 Hz) lateralized in the EEG. CSF with normal count of protein and normal count of White blood cells and elevated count of total tau 1200 (normal range Conclusions Even though a definite diagnosis of Creutzfeldt-Jacob disease (CJD) can only be manifest by brain autopsy or biopsy post mortem a possible or likely diagnosis can be established combining CSF markers, brain imaging and EEG. This case illustrates the importance of EEG and especially consecutive EEGs in the diagnostic process of rapidly progressive dementia.

Early signs of middle cerebral artery infarction on multidetector computed tomography: Review of 20 cases.

OBJECTIVE:This study intended to assess the occurrence of early signs of middle cerebral artery (MCA) on multidetector computed tomography (MDCT) in correlation with duration of the clinical features of stroke.PATIENTS AND METHODS:This retrospective study analyzed the electronic records of 20 patients with MCA infarction. The detected signs studied according to the onset of the clinical features of stroke to the time of CT imaging.RESULTS:Out of 20 patients with MCA infarction included in this study, the results revealed a significant relationship between the presence of insular ribbon sign and/or subtle hypodensity and hyperacute infarction (P < 0.001 and 0.003, respectively). Results revealed significant relationship between the occurrence of hypodense area, effacement of the cortical sulci, and compression of the ipsilateral lateral ventricle with acute infarction (6–72 h), (P = 0.006, 0.007, and 0.002) (odds ratio = 0.047, 0.050 and 0.028) and (95% confidence interval = 0.004–0.552, 0.004–0.597 and 0.002–0.367) respectively.CONCLUSION:MDCT can detect nearly half of MCA infarctions in the first 6 h. Insular ribbon sign and subtle hypodensity were the most significant findings in the first 6 h of stroke. Hypodense area was a significant sign after 6 h. Diabetes mellitus and ischemic heart disease were the most common risk factors. Hemiparesis was the most common clinical finding in MCA infarction.

Clinical, neuroimaging and genetic features of two Chinese families with fatal familial insomnia

Objective: To examine clinical, neuroimaging and genetic features of two Chinese families with fatal familial insomnia (FFI). Methods: The clinical data, including case history, physical examination, biochemical analysis of blood and neuroimaging of two pedigrees with FFI who admitted to the Navy General Hospital in 2014 and 2017 were collected. The D178N prion protein (PRNP) mutation were determined by DNA sequencing among the proband and family members. Results: There were 6 patients in 2 families, 5 male and 1 female. The onset age of disease in family 1 was 47 and 60 years old respectively, and 46, 58, 58, 60 years old respectively in family 2. In terms of disease course, patients in family 1 had a rapid disease course and died half year after onset while patients in family 2 had a relatively slow disease course and survived more than 1 year after onset.The induced factors of the patients in the family 1 were fright, followed by abnormal behaviors and sleep disorders accompanied by autonomic nervous dysfunction; the clinical features of the pedigree 2 were memory loss, decreased sleep and motor disorder without obvious inducement, and the autonomic nervous dysfunction was not significant. The neuroimaging examination of 2 probands showed a mild atrophy of the whole brain and no ribbon sign. The electroencephalography (EEG) did not show typical triphasic waves. Both cases had a positive cerebrospinal fluid (CSF) 14-3-3 protein and PrP D178N /Met-129 mutation.All patients were given traditional sedatives or anti-anxiety and depression drugs which were with poor efficacy. Conclusions: The major clinical manifestations of FFI are sleep disorders accompanied by mental disorders. The clinical manifestations are similar among different individuals within one family, however, there is obvious clinical variability among different families. The neuroimaging examination shows a mild atrophy of the whole brain and no ribbon sign. There are no typical triphasic waves in EEG. Positive CSF 14-3-3 protein and PrP D178N /Met-129 mutation are common in FFI. Traditional sedatives or anti-anxiety and depression drugs may have poor efficacy.

The ribbon sign.

The ribbon sign.