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

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.

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Real-time Quaking-induced Conversion Assay for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease in a Living Patient

Infectious Diseases Research and Treatment ◽

10.1177/1178633719874797 ◽

2019 ◽

Vol 12 ◽

pp. 117863371987479 ◽

Cited By ~ 1

Author(s):

Vikas D Reddy ◽

Almutasem Hamed ◽

Neesha Settipalle ◽

Suraj Jande ◽

Sabih Rahman ◽

...

Keyword(s):

Real Time ◽

Prion Protein ◽

Surrogate Marker ◽

Brain Biopsy ◽

Postmortem Brain ◽

Mri Findings ◽

Progressive Dementia ◽

Ataxic Gait ◽

Clinical Criteria ◽

Jakob Disease

Creutzfeldt-Jakob disease (CJD) is the most common prion disease in humans with an incidence of one case per million inhabitants worldwide. The sporadic form of CJD (sCJD) is spontaneous and accounts for 85% of cases. Its symptoms include rapidly progressive dementia, ataxic gait, personality changes, myoclonus, coma, and eventually death. The challenging diagnosis is currently made by a combination of clinical criteria and supporting tests such as electroencephalography (EEG), magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) studies. These modalities can be falsely positive or negative in some cases. Therefore, true confirmation usually requires a postmortem brain biopsy. We present a case of a 58-year-old woman who was diagnosed with sporadic form CJD by the novel Real-time Quaking-induced Conversion (RT-QuIC) assay. It is based on an ultrasensitive detection of the pathogenic prion protein in the CSF that directly detects a prion protein rather than a surrogate marker of neurodegeneration such as 14-3-3 or tau protein. The RT-QuIC assay has emerged as the most sensitive and specific CSF study to accurately diagnose sCJD in a living patient, without the need for invasive brain biopsy. The emergence of the nasal brushing RT-QuIC assay may further revolutionize the future of combating prion diseases.

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Evaluation of Incidence and Clinical Features of Antibody-Associated Autoimmune Encephalitis Mimicking Dementia

Behavioural Neurology ◽

10.1155/2014/935379 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 10

Author(s):

Arzu Çoban ◽

Cem İsmail Küçükali ◽

Başar Bilgiç ◽

Nazlı Yalçınkaya ◽

Hazal Haytural ◽

...

Keyword(s):

Clinical Features ◽

Lewy Bodies ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Autoimmune Encephalitis ◽

Clinical Findings ◽

Acid Decarboxylase ◽

Sleep Behavior ◽

Clinical Criteria ◽

Dementia Patients

Background. Anti-neuronal autoimmunity may cause cognitive impairment that meets the criteria for dementia.Objective. Our aim was to detect the incidence and clinical features of autoimmune encephalitis imitating clinical findings of primary dementia disorders and to delineate the validity of anti-neuronal antibody screening in dementia patients.Methods. Fifty consecutive patients fulfilling the clinical criteria for primary dementia, 130 control patients, and 50 healthy controls were included. Their sera were investigated for several ion channel and glutamic acid decarboxylase (GAD) antibodies by a cell-based assay, radioimmunoassay, and ELISA, as required.Results. Sixteen patients satisfying dementia criteria had atypical findings or findings suggestive of autoimmune encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibody was detected in a patient with dementia, Parkinsonism, and REM sleep behavior disorder (RBD) fulfilling the criteria for dementia with Lewy bodies (DLB). One control patient with bipolar disease displayed low anti-GAD antibody levels.Conclusions. Our study showed for the first time the presence of parkinsonism and RBD in an anti-NMDAR encephalitis patient mimicking DLB. Although autoimmune encephalitis patients may occasionally present with cognitive decline, most dementia patients do not exhibit anti-neuronal antibodies, suggesting that routine analysis of these antibodies in dementia is not mandatory, even though they display atypical features.

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Applicability of long-term electroencephalography in pre-mortem diagnosis of Creutzfeldt–Jakob disease: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x17744482 ◽

2017 ◽

Vol 5 ◽

pp. 2050313X1774448 ◽

Cited By ~ 2

Author(s):

Sanaz Attaripour Isfahani ◽

Michelle Dougherty ◽

Gediminas Peter Gliebus

Keyword(s):

Cerebrospinal Fluid ◽

Symptom Onset ◽

Epileptiform Activity ◽

Progressive Dementia ◽

Clinical Criteria ◽

Fluid Analysis ◽

Weighted Magnetic Resonance Imaging ◽

Jakob Disease ◽

Rapid Cognitive Decline

Creutzfeldt–Jakob disease accounts for more than 90% of all sporadic prion disease cases. The molecular MM2 genotype has been divided into cortical and thalamic subtypes based on structures involved and is characterized clinically by progressive dementia without ataxia or typical electroencephalography changes. Proposed diagnostic criteria for MM2 cortical type sporadic Creutzfeldt–Jakob disease include progressive dementia, cortical hyper-intensity on diffusion-weighted magnetic resonance imaging, increased cerebrospinal fluid 14-3-3 protein level, and the exclusion of other types of dementia. The presence of periodic discharges on electroencephalography in MM2 cortical type were reported in 42% of the cases. We are reporting a case of sporadic Creutzfeldt–Jakob disease cortical MM2-type presenting with rapid cognitive decline, who survived 8 months since symptom onset. Brain imaging, cerebrospinal fluid analysis, and long-term electroencephalography monitoring were obtained and diagnosis was confirmed by autopsy. Short-term electroencephalography recording, performed 5 months after symptom onset, demonstrated diffuse background slowing without epileptiform activity. Long-term video electroencephalography monitoring demonstrated generalized slowing, maximum in bilateral frontal areas, which intermittently would become rhythmic (1–2 Hz) without hemispheric predominance. If the findings do not clearly meet the proposed clinical criteria for sporadic Creutzfeldt–Jakob disease, the use of long-term electroencephalography could increase the sensitivity. We question whether the lack of the characteristic findings on electroencephalography in some cases could be due to insufficient time of recording. Application of long-term electroencephalography monitoring increases the sensitivity of electroencephalography and the certainty of pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease.

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Is there a link between COVID-19 and Creutzfeldt-Jakob Disease? a Case Report

Journal of Research in Clinical Medicine ◽

10.34172/jrcm.2021.026 ◽

2021 ◽

Vol 9 (1) ◽

pp. 26-26

Author(s):

Ehsan Nasiri ◽

Amirreza Naseri ◽

Mohammad Yazdchi ◽

Mahnaz Talebi

Keyword(s):

Protein Detection ◽

Behavioral Changes ◽

Resonance Imaging ◽

Mri Findings ◽

Progressive Dementia ◽

Abnormal Signal ◽

Jakob Disease ◽

The Central Nervous System ◽

Abnormal Signal Intensity ◽

Magnetic Resonance Imaging Mri

Creutzfeldt-Jakob Disease (CJD) is a rare rapidly progressive neurodegenerative disease. The diagnosis of CJD is based on magnetic resonance imaging (MRI) findings, electro-encephalography (EEG), or 14-3-3 protein detection. We report a case of a previously-healthy 72 years old woman, with evidence of coronavirus disease 2019 (COVID-19), who complained of behavioral changes and rapidly progressive dementia. While hospitalization, she didn't have orientation to time and place and repeated an irrelevant sentence in response to questions. Also, anomia and impaired comprehension was observed. Myoclonic jerks, abnormal signal intensity at bilateral parieto-occipital cortices in MRI, periodic sharp wave complexes in EEG, and increased lactate dehydrogenase in cerebrospinal fluid (CSF), highly recommended CJD for her. This is the second case of CJD after COVID-19 during this pandemic, which can be an alarm to clinicians about the silent impact of COVID-19 on the central nervous system.

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Spectrum of clinical features and neuroimaging findings in acute cerebral infarction patients with unusual ipsilateral motor impairment– a series of 22 cases

BMC Neurology ◽

10.1186/s12883-019-1516-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Zhe-Ren Tan ◽

Chen Zhang ◽

Fa-Fa Tian

Keyword(s):

Cerebral Infarction ◽

Clinical Features ◽

Corticospinal Tract ◽

Past History ◽

Motor Impairment ◽

Cortical Reorganization ◽

Motor Dysfunction ◽

Cerebral Injury ◽

Mri Findings ◽

History Of

Abstract Background Cerebral infarction occurs when the arteries to brain are obstructed, and motor impairment contralateral to responsible lesion is commonly recognized. Few studies have profiled the characteristics of cases with ipsilateral motor impairment. We sought to characterize clinical features of patients with motor dysfunction caused by ipsilateral ischemic stroke. Methods We retrieved and analyzed the medical data for patients with ipsilateral cerebral infarction. Patients were regarded as having ipsilateral cerebral infarction if motor impairment is ipsilateral to recent stroke lesions. Results Only 22 patients with unusual ipsilateral cerebral infarction were included in this study. Ipsilateral limb paralysis was observed in all cases, and one case showed central facioplegia. Majority of patients with limb paralysis (90.9%, 20/22) presented with mild muscle strength deficits (MRC grading of 4 or more). Most of the patients (72.7%, 16/22) had a past history of stroke, and previous strokes were contralateral to the side of the recent stroke in 14 out of 16 patients (87.5%). No history of stroke or cerebral injury was identified in seven patients. With aspect of MRI findings, recent infarct lesions of all cases were located along the corticospinal tract. Conclusions History of stroke plays an important role in the pathogenesis of ipsilateral motor impairment, and cortical reorganization in the unaffected hemisphere may contribute to the compensation of motor function after stroke. Besides that, some cases with first stroke may be due to impairment of ipsilateral uncrossed corticospinal fibers.

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An Evaluation of Rapidly Progressive Dementia Culminating in a Diagnosis of Creutzfeldt–Jakob Disease

Case Reports in Infectious Diseases ◽

10.1155/2018/2374179 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Parmvir Parmar ◽

Curtis L. Cooper ◽

Daniel Kobewka

Keyword(s):

Differential Diagnosis ◽

Cognitive Deficits ◽

Autoimmune Encephalitis ◽

Illustrative Case ◽

Visual Hallucinations ◽

Progressive Dementia ◽

History Of ◽

Jakob Disease ◽

Clinical Description ◽

Sporadic Cjd

Rapidly progressive dementia is a curious and elusive clinical description of a pattern of cognitive deficits that progresses faster than typical dementia syndromes. The differential diagnosis and clinical workup for rapidly progressive dementia are quite extensive and involve searching for infectious, inflammatory, autoimmune, neoplastic, metabolic, and neurodegenerative causes. We present the case of a previously highly functional 76-year-old individual who presented with a 6-month history of rapidly progressive dementia. His most prominent symptoms were cognitive impairment, aphasia, visual hallucinations, and ataxia. Following an extensive battery of tests in hospital, the differential diagnosis remained probable CJD versus autoimmune encephalitis. He clinically deteriorated and progressed to akinetic mutism and myoclonus. He passed away 8 weeks after his initial presentation to hospital, and an autopsy confirmed a diagnosis of sporadic CJD. We use this illustrative case as a framework to discuss the clinical and diagnostic considerations in the workup for rapidly progressive dementia. We also discuss CJD and autoimmune encephalitis, the two main diagnostic possibilities in our patient, in more detail.

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Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2001000200001 ◽

2001 ◽

Vol 59 (2A) ◽

pp. 161-164 ◽

Cited By ~ 16

Author(s):

Ricardo Nitrini ◽

Luís Sidônio Teixeira da Silva ◽

Sérgio Rosemberg ◽

Paulo Caramelli ◽

Paulo Eduardo Mestrinelli Carrilho ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Clinical Features ◽

Prion Disease ◽

Prion Diseases ◽

Age At Onset ◽

Abnormal Behavior ◽

Chromosome 17 ◽

Progressive Dementia ◽

Behavioral Disturbances ◽

Presenting Symptoms

OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD), the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

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Clinical Heterogeneity in Acute Symptomatic Seizures due to Autoimmune Encephalitis Related to GAD65 Antibodies

NeuroImmunoModulation ◽

10.1159/000519229 ◽

2021 ◽

pp. 1-6

Author(s):

Xuemei Fan ◽

Xinxin Li ◽

Shuai Wang ◽

Yafei Zhu ◽

Songyan Liu ◽

...

Keyword(s):

Clinical Features ◽

Brain Mri ◽

Autoimmune Encephalitis ◽

Mri Findings ◽

Ocular Movement ◽

Symptomatic Seizures ◽

Gad 65 ◽

Gad 65 Antibodies ◽

Acute Symptomatic Seizures ◽

Gad65 Antibodies

Introduction: This study aimed to explore the diversity and clinical features of acute symptomatic seizures due to autoimmune encephalitis related to anti-glutamate decarboxylase (GAD) 65 antibodies. Methods: Clinical data of a series of 6 patients positive for anti-GAD65 antibodies were retrospectively analyzed. Results: Five of the patients were male and 1 was a female, with a median age of 44.1 years (range 18–70 years). Seizure forms were varied in 6 patients when they were admitted to the hospital: 3 cases of seizures only and 3 accompanied by other symptoms, such as mental disorder, cognitive impairment, cerebellar ataxia, and ocular movement disorder. Three patients (50%) had coexisting systemic autoimmune diseases, including diabetes mellitus, vitiligo, and hyperthyroidism. Five patients (83%) had abnormal brain MRI findings. They were all treated by immunotherapy, 5 of 6 patients improved significantly but relapsed after withdrawing methylprednisolone, and 1 patient got deteriorated. None of them were diagnosed with tumors. Conclusions: Clinical features of acute symptomatic seizures related to GAD65 antibodies are diverse, and early and continuous immunotherapy is necessary for patients.

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Sporadic Creutzfeldt Jakob Disease: A Patient with Dementia and Involuntary Movement Myoclonus

Journal of Armed Forces Medical College Bangladesh ◽

10.3329/jafmc.v12i2.41111 ◽

2016 ◽

Vol 12 (2) ◽

pp. 141-144

Author(s):

Mohd Mozibor Rahman ◽

Sanzida Akhter ◽

Noor E Jabeen

Keyword(s):

Histopathological Examination ◽

Involuntary Movement ◽

Armed Forces ◽

University Hospital ◽

Mri Findings ◽

Progressive Dementia ◽

Diagnostic Features ◽

Extrapyramidal Signs ◽

National University ◽

Jakob Disease

Creutzfeldt Jakob Disease (CJD) is an incurable, invariably fatal, rapidly progressive neurodegenerative disease caused by an abnormal isoform of a cellular glycoprotein known as the prion protein. CJD occurs worldwide, estimated annual incidence is about one case per million populations per year. Sporadic (sCJD) is a human prion disease; infection with this disease usually leads to death within one year of onset of illness. The characteristic clinical and diagnostic features of rapidly progressive dementia, myoclonus, visual or cerebellar signs, pyramidal and extrapyramidal signs, akinetic mutism and positive result on the presence of 14-3-3 protein in CSF assay, typical EEG features and MRI findings of brain are highly suggestive of diagnosis. Biopsy of brain for histopathological examination is more specific and confirmatory for diagnosis. This article reports a 65 years old lady of sCJD who was diagnosed by characteristic findings of MRI of brain, Electro-encephalography (EEG) and cerebrospinal fluid (CSF) assay at National University Hospital (NUH) Singapore and now admitted at United Hospital Limited (UHL) Dhaka for palliative and supportive management Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 141-144

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EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex–Associated Autoimmune Encephalitis and Creutzfeldt-Jakob Disease

Clinical EEG and Neuroscience ◽

10.1177/1550059418774686 ◽

2018 ◽

Vol 50 (2) ◽

pp. 121-128

Author(s):

Brin Freund ◽

John C. Probasco ◽

Mackenzie C. Cervenka ◽

Raoul Sutter ◽

Peter W. Kaplan

Keyword(s):

Potassium Channel ◽

Medical Records ◽

Medical Center ◽

Autoimmune Encephalitis ◽

Response To Treatment ◽

Johns Hopkins Hospital ◽

Progressive Dementia ◽

Voltage Gated ◽

Sharp Wave ◽

Jakob Disease

Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex–associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly detected in CJD, and tau levels were higher in those with CJD ( P < .006). On neuroimaging, diffusion restriction in the cortex ( P = .001), caudate ( P < .001), and putamen ( P = .001) was more frequent in CJD. Periodic sharp wave complexes ( P = .001) and generalized suppressed activity ( P = .008) were more common on initial EEG in CJD. On serial EEGs, generalized periodic discharges ( P = .004), generalized suppressed activity (P=0.008), and periodic sharp wave complexes ( P < .001) were detected more in CJD. This study shows that there are a number of differentiating features between CJD and VGKC AE, and electroencephalography can aid in their diagnoses. Performing serial EEGs better delineates these conditions.

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