scholarly journals Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

2020 ◽  
Author(s):  
Akin Nihat ◽  
Tze How Mok ◽  
Hans Odd ◽  
Andrew Thompson ◽  
Diana Caine ◽  
...  
Keyword(s):  
Disease Severity ◽  
Cognitive Dysfunction ◽  
Clinical Examination ◽  
Rating Scales ◽  
Phenotypic Heterogeneity ◽  
Motor Dysfunction ◽  
Longitudinal Change ◽  
Progressive Dementia ◽  
Clinical Change ◽  
Jakob Disease

AbstractObjectiveSporadic Creutzfeldt-Jakob disease (sCJD) causes rapidly-progressive dementia and complex abnormalities of motor systems with striking phenotypic heterogeneity, but no tools are available for the clinician to determine disease severity from bedside cognitive and neurological assessments. We used a robust statistical methodology and routinely-collected examination data to develop and validate short clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sCJD.MethodsWe undertook a retrospective analysis of clinical examination data from the prospective National Prion Monitoring Cohort study, October 2008 – December 2016. Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurological and cognitive examination tests.A longitudinal clinical examination dataset was constructed from a total of 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores, over 130 patient-years of study, and used to demonstrate scale utility.ResultsThe Rasch-derived Motor Scale consists of 8 items, including examination items reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform consistently regardless of age or gender and have excellent inter-rater reliability. Each scale can be completed in a few minutes at the bedside, as part of a normal neurocognitive examination. Several uses of the scales, in measuring longitudinal change, prognosis, and phenotypic heterogeneity are illustrated.InterpretationThese two novel scales measuring motor and cognitive dysfunction in sCJD should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly-progressive, multisystem conditions with limited longitudinal follow-up.

scholarly journals Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

2022 ◽  
pp. jnnp-2021-327722
Author(s):  
Akin Nihat ◽  
Tze How Mok ◽  
Hans Odd ◽  
Andrew Geoffrey Bourne Thompson ◽  
Diana Caine ◽  
...  
Keyword(s):  
Clinical Examination ◽  
Rating Scales ◽  
Statistical Approach ◽  
Motor Dysfunction ◽  
Longitudinal Change ◽  
Clinical Change ◽  
Scale Scores ◽  
Jakob Disease ◽  
Function Language

ObjectiveTo use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.MethodsRasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008–December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility.ResultsThe Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated.ConclusionsThese two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up.

scholarly journals P.009 Improving Detection of Creutzfeldt-Jakob Disease Mimics in Clinical Practice

2021 ◽  
Vol 48 (s3) ◽  
pp. S22-S22
Author(s):  
ES Lazar ◽  
AL Porter ◽  
CC Prusinski ◽  
S Dunham ◽  
A Lopez-Chiriboga ◽  
...  
Keyword(s):  
Clinical Features ◽  
Autoimmune Encephalitis ◽  
Motor Dysfunction ◽  
Mri Findings ◽  
Progressive Dementia ◽  
Clinical Criteria ◽  
Presenting Symptoms ◽  
Jakob Disease ◽  
Study Sites ◽  
Motor Abnormalities

Background: Assays capable of detecting prions in CSF (e.g., RT-QuIC) have greatly improved the antemortem diagnosis of Creutzfeldt-Jakob disease (CJD) yet take time to conduct and are not widely accessible. There is a need to identify clinical features and common tests that identify mimics at presentation. Methods: Mimics were identified within longitudinal studies of rapidly progressive dementia at study sites. Mimics met clinical criteria for probable CJD but did not have CJD. Clinical features were compared between mimics and patients with CJD assessed at Mayo Clinic Enterprise (n=79) and Washington University in St. Louis (n=10; Jan-2014 to Oct-2020). Results: Mimics (10/155; 6.5%) were diagnosed with autoimmune encephalitis (n=7), neurosarcoidosis, frontotemporal lobar degeneration with motor neuron disease, and unknown dementia. Age-at-symptom onset, gender, presenting symptoms, and EEG and MRI findings were similar between mimics and CJD patients. Focal motor abnormalities (49/93, 10/10), elevations in CSF leukocytosis (4/92, 5/10) and protein (39/92, 9/10) were more common in mimics (p<0.01). Neural-specific autoantibodies associated with autoimmune encephalitis were detected within the serum (4/9) and CSF (5/10) of mimics, but not CJD cases. Conclusions: Autoimmune encephalitis, neurosarcoidosis and neurodegenerative diseases may mimic CJD at presentation and should be considered in patients with early motor dysfunction and abnormal CSF studies.

scholarly journals A Case of Familial Creutzfeldt-Jakob Disease Presenting with Dry Cough

2006 ◽  
Vol 33 (2) ◽  
pp. 243-245 ◽  
Author(s):  
Sandrine Larue ◽  
Steve Verreault ◽  
Peter Gould ◽  
Michael B. Coulthart ◽  
Catherine Bergeron ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Mutation Screening ◽  
Disease Onset ◽  
Visual Hallucinations ◽  
Progressive Dementia ◽  
Gene Encoding ◽  
Progressive Ataxia ◽  
Persistent Cough ◽  
Jakob Disease ◽  
Classical Triad

ABSTRACT:Background:Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is based on the classical triad of rapidly progressive dementia, myoclonus and abnormal EEG. The 200k mutation within the gene encoding PrP, located on the short arm of chromosome 20, accounts for more than 70% of families with CJD worldwide.Case Report:Herein, we report a patient who developed persistent dry cough and classical signs of CJD, including severe cognitive decline, cerebellar signs, and myoclonic jerks, leading to death a few weeks after disease onset. Mutation screening showed that he had the 200k point mutation in the PRNP gene. His mother had died twenty years earlier with neuropathologically confirmed CJD. She had presented a rapidly progressive ataxia with myoclonus, dementia, visual hallucinations, and the same persistent dry cough.Conclusions:The clinical presentation of this familial CJD case with persistent dry cough is quite unusual. Therefore, a neurological etiology should be sought when confronted with an unexplained persistent cough.

Deep Learning Representation from Electroencephalography of Early-Stage Creutzfeldt-Jakob Disease and Features for Differentiation from Rapidly Progressive Dementia

2016 ◽  
Vol 27 (02) ◽  
pp. 1650039 ◽  
Author(s):  
Francesco Carlo Morabito ◽  
Maurizio Campolo ◽  
Nadia Mammone ◽  
Mario Versaci ◽  
Silvana Franceschetti ◽  
...  
Keyword(s):  
Deep Learning ◽  
Supervised Learning ◽  
Early Stage ◽  
Processing System ◽  
Fine Tuning ◽  
Permutation Entropy ◽  
Support Vector ◽  
Progressive Dementia ◽  
Time Frequency ◽  
Jakob Disease

A novel technique of quantitative EEG for differentiating patients with early-stage Creutzfeldt–Jakob disease (CJD) from other forms of rapidly progressive dementia (RPD) is proposed. The discrimination is based on the extraction of suitable features from the time-frequency representation of the EEG signals through continuous wavelet transform (CWT). An average measure of complexity of the EEG signal obtained by permutation entropy (PE) is also included. The dimensionality of the feature space is reduced through a multilayer processing system based on the recently emerged deep learning (DL) concept. The DL processor includes a stacked auto-encoder, trained by unsupervised learning techniques, and a classifier whose parameters are determined in a supervised way by associating the known category labels to the reduced vector of high-level features generated by the previous processing blocks. The supervised learning step is carried out by using either support vector machines (SVM) or multilayer neural networks (MLP-NN). A subset of EEG from patients suffering from Alzheimer’s Disease (AD) and healthy controls (HC) is considered for differentiating CJD patients. When fine-tuning the parameters of the global processing system by a supervised learning procedure, the proposed system is able to achieve an average accuracy of 89%, an average sensitivity of 92%, and an average specificity of 89% in differentiating CJD from RPD. Similar results are obtained for CJD versus AD and CJD versus HC.

scholarly journals Slow Motion Analysis of Repetitive Tapping (SMART) Test: Measuring Bradykinesia in Recently Diagnosed Parkinson’s Disease and Idiopathic Anosmia

2021 ◽  
pp. 1-15
Author(s):  
Cristina Simonet ◽  
Miquel A. Galmes ◽  
Christian Lambert ◽  
Richard N. Rees ◽  
Tahrina Haque ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scales ◽  
Early Stage ◽  
Slow Motion ◽  
Motor Dysfunction ◽  
Prodromal Phase ◽  
Floor Effect ◽  
Cross Sectional ◽  
Early Stages

Background: Bradykinesia is the defining motor feature of Parkinson’s disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. Objective: To develop a quantitative method to track repetitive tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia. Methods: This was a cross-sectional study of 99 participants (early-stage PD = 26, controls = 64, idiopathic anosmia = 9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per second. From each video, amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second) was extracted. Clinical assessment was based on the motor section of the MDS-UPDRS. Results: People in the early stage of PD performed the task with slower velocity (p <  0.001) and with greater frequency slope than controls (p = 0.003). The combination of reduced velocity and greater frequency slope obtained the best accuracy to separate early-stage PD from controls based on metric thresholds alone (AUC = 0.88). Individuals with anosmia exhibited slower velocity (p = 0.001) and smaller amplitude (p <  0.001) compared with controls. Conclusion: We present a simple, proof-of-concept method to detect early motor dysfunction in PD. Mean tap velocity appeared to be the best parameter to differentiate patients with PD from controls. Patients with anosmia also showed detectable differences in motor performance compared with controls which may suggest that some are in the prodromal phase of PD.

Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease

2018 ◽  
Vol 18 (2-3) ◽  
pp. 127-132 ◽  
Author(s):  
Jeong-Yoon Lee ◽  
Ji Sun Kim ◽  
Wooyoung Jang ◽  
Jinse Park ◽  
Eungseok Oh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
White Matter ◽  
Parkinson Disease ◽  
Cognitive Dysfunction ◽  
Rating Scale ◽  
White Matter Lesions ◽  
Motor Dysfunction ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

Rapidly Progressive Dementia and Coma

2019 ◽  
pp. 704-712
Author(s):  
Prasuna Kamireddi ◽  
Jason L. Siegel ◽  
Dennis W. Dickson
Keyword(s):  
Intensive Care Unit ◽  
Functional Ability ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Cognitive Domain ◽  
Progressive Dementia ◽  
Common Causes ◽  
Jakob Disease ◽  
Clinical Signs And Symptoms ◽  
Definition Of

In most patients with dementia, the clinical signs and symptoms progress gradually over many years. However, neurointensivists may encounter patients who have rapidly progressive dementia (RPD). Often these patients need to be admitted to the intensive care unit for management of status epilepticus, agitation, or ventilation in coma. Although the prototype of RPD is Creutzfeldt-Jakob disease, this chapter reviews other common causes of RPD. An established definition of RPD does not exist, but in this chapter RPD refers to the loss of more than 1 cognitive domain and functional ability, usually occurring over a few months.

scholarly journals Doença de Creutzfeldt-Jakob: Apresentação Atípica de uma Doença Muito Rara

2020 ◽  
Vol 33 (13) ◽  
Author(s):  
Renato Oliveira ◽  
Marta Dias ◽  
Inês Brás Marques
Keyword(s):  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Diffusion Weighted Imaging ◽  
Negative Symptoms ◽  
Sudden Onset ◽  
Lower Limbs ◽  
Progressive Dementia ◽  
Radiological Features ◽  
Diffusion Weighted ◽  
Jakob Disease

Creutzfeldt-Jakob disease typically presents as rapidly progressive dementia. We describe the case of a 59-year-old male patient presenting with sudden onset of central facial palsy and dysarthria, followed by myoclonus of his left upper and lower limbs. Initial brain magnetic resonance showed hyperintensity of the right caudate and putamen on diffusion-weighted imaging and T2 sequences. Cerebrospinal fluid analysis showed increased protein count. The workup to investigate autoimmune, infectious and paraneoplastic causes was negative. Symptoms progressively worsened, with left hemiplegia, dysphagia, urinary incontinence, and, later, akinetic mutism. The follow-up brain magnetic resonance scan revealed hyperintensity of bilateral basal ganglia as well as cerebral cortical abnormalities on diffusion-weighted imaging. Electroencephalography showed periodic activity and tau protein levels in the cerebrospinal fluid were elevated. Genetic analysis showed mutation c-598G > A. The patient died four months later. We report a case of familial Creutzfeldt-Jakob disease with atypical clinical and radiological features, namely neurological focal signs with sudden onset, absence of significant cognitive impairment and unilateral radiological findings. With disease progression, characteristic clinical and radiological features led to the diagnosis.

Sporadic Creutzfeldt-Jakob disease: a description of two cases

2012 ◽  
Vol 24 (7) ◽  
pp. 1183-1185 ◽  
Author(s):  
Kavita Das ◽  
Rebecca Davis ◽  
Brett DuToit ◽  
Brian Parsons
Keyword(s):  
Disease Process ◽  
Coordinated Care ◽  
Progressive Dementia ◽  
Spongiform Encephalopathies ◽  
Delivery Of Care ◽  
Central Nervous System Dysfunction ◽  
Jakob Disease ◽  
Multiple Challenges ◽  
The Uk ◽  
Adequate Management

ABSTRACTSporadic Creutzfeldt-Jakob disease (sCJD) is a rare and devastating illness. It is the most frequently encountered form of the spongiform encephalopathies with 50 new cases a year in the UK. It presents with a myriad of symptoms reflecting central nervous system dysfunction and is characterized by a rapidly progressive dementia leading to death. The disease process can pose multiple challenges: diagnostic conundrums, complexities in management, and palliative care issues. Good coordinated care between services and information is paramount in adequate management and delivery of care for patients suffering from sCJD.Psychiatry services frequently become involved in the assessment and management of sCJD.

scholarly journals A Corticobasal Syndrome Variant of Familial Creutzfeldt-Jakob Disease with Stroke-Like Onset

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Ján Necpál ◽  
Martin Stelzer ◽  
Silvia Koščová ◽  
Michal Patarák
Keyword(s):  
Corticobasal Degeneration ◽  
Early Death ◽  
Prnp Gene ◽  
Corticobasal Syndrome ◽  
Progressive Dementia ◽  
Rare Presentation ◽  
Alien Hand ◽  
Jakob Disease ◽  
Neurological Features ◽  
Characteristic Features

Creutzfeldt-Jakob disease (CJD) is an untreatable rare human prion disease characterized by rapidly progressive dementia along with various neurological features, including myoclonus and sometimes other movement disorders. The clinical course is typically insidious and rapid, leading to an early death. In general, the most common form is sporadic CJD; however, Slovakia is typical for a high percentage of genetic cases. We present an unusual case report of a 65-year-old man with a sudden, stroke-like onset of motor aphasia with right-sided levodopa unresponsive parkinsonism, alien hand, and other characteristic features of corticobasal syndrome (CBS), with rapid deterioration and death on the 32nd day of the disease. Various neurodegenerative disorders are manifested with CBS as a clinical phenotype, including corticobasal degeneration (CBD), progressive supranuclear palsy, Alzheimer’s disease, and CJD. In our patient, mutation E200K and M129M polymorphism of the PRNP gene and typical immunohistochemical findings pointed to a diagnosis of CJD. The patient’s mother died of CJD many years ago. Several CBS-CJD cases were described, but the atypical stroke-like onset of CBS-CJD, an extremely rare presentation of CJD, makes our case unique worldwide.

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