High Incidence of Sporadic Creutzfeldt-Jakob Disease in Slovenia in 2015: A Case Series

Background: Creutzfeldt-Jakob disease (CJD) is a rare fatal neurodegenerative disorder presenting with rapid cognitive decline and additional signs. The clinical characteristics of an increasing number of sporadic CJD (sCJD) patients admitted to the Ljubljana University Medical Centre are presented as well as the incidence of sCJD in Slovenia in 2015 compared to previous years. Methods: We investigated patients presenting with rapidly progressive dementia and at least one additional sign. The diagnosis was made based on clinical diagnostic criteria and an autopsy was performed in all cases. Data on definite sCJD cases in Slovenia since 1999 were obtained and its incidence was calculated. Results: Eight patients with definite sCJD died in 2015 in Slovenia (incidence: 3.89 cases per million). The long-term incidence 1999 was 1.67 per million. Conclusions: The incidence of sCJD was considerably higher in 2015. It reflects fluctuations in sporadic cases of this rare disease. The rising trend might indicate a previous underestimation and better recognition of the disease.

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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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An unusual presentation of sporadic Creutzfeldt-Jakob disease

Age and Ageing ◽

10.1093/ageing/afaa013 ◽

2020 ◽

Vol 49 (3) ◽

pp. 490-492

Author(s):

Hannah Podger ◽

Anil Ipe

Keyword(s):

Language Impairment ◽

Neurodegenerative Disorder ◽

Case Reports ◽

Clinical Signs ◽

Unusual Presentation ◽

Progressive Dementia ◽

Extrapyramidal Signs ◽

Jakob Disease ◽

Sporadic Cjd ◽

Visual Disturbances

Abstract Sporadic Creutzfeld-Jakob disease (CJD) is a rare neurodegenerative disorder. It is uniformly fatal. Clinical signs include myoclonus, visual disturbances, cerebellar ataxia, akinetic mutism and pyramidal/extrapyramidal signs in addition to a rapidly progressive dementia. Premortem diagnosis is challenging due to the rarity of the condition and the subsequent low index of suspicion held for it. On literature review, isolated language impairment as the first neurological symptom occurs in only about 1% of patients with sporadic CJD (El Tawil et al. (2017, Acta Neurol Scand, 135: 316–23)). We present this patient’s case, marked for the unusual presentation and the rapidity of decline, to emphasise the need for awareness of CJD as an important differential diagnosis on stroke units. In our case, magnetic resonance imaging findings drove the suspicion of sporadic CJD as the diagnosis. This seems to correlate with other case reports recognising CJD presenting with progressive aphasic disorders (Terrin et al. (2017, Neurol Sci, 38: 1535–7); Mandell et al. (1989, Neurology, 39: 55–8); Martory et al. (2012, Eur Neurol, 67: 360–2)).

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Fucosidosis—Clinical Manifestation, Long-Term Outcomes, and Genetic Profile—Review and Case Series

Genes ◽

10.3390/genes11111383 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1383 ◽

Cited By ~ 1

Author(s):

Karolina M. Stepien ◽

Elżbieta Ciara ◽

Aleksandra Jezela-Stanek

Keyword(s):

Neurodegenerative Disorder ◽

Respiratory Infections ◽

Clinical Manifestations ◽

Case Series ◽

Genetic Profile ◽

Nonsense Mutations ◽

Pathogenic Variants ◽

One Stop ◽

Stop Loss

Fucosidosis is a neurodegenerative disorder which progresses inexorably. Clinical features include coarse facial features, growth retardation, recurrent upper respiratory infections, dysostosis multiplex, and angiokeratoma corporis diffusum. Fucosidosis is caused by mutations in the FUCA1 gene resulting in α-L-fucosidase deficiency. Only 36 pathogenic variants in the FUCA1 gene are related to fucosidosis. Most of them are missense/nonsense substitutions; six missense and 11 nonsense mutations. Among deletions there were eight small and five gross changes. So far, only three splice site variants have been described—one small deletion, one complete deletion and one stop-loss mutation. The disease has a significant clinical variability, the cause of which is not well understood. The genotype–phenotype correlation has not been well defined. This review describes the genetic profile and clinical manifestations of fucosidosis in pediatric and adult cases.

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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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Intracranial Procedures and Expected Frequency of Creutzfeldt-Jakob Disease

Neuroepidemiology ◽

10.1159/000441032 ◽

2015 ◽

Vol 46 (1) ◽

pp. 1-8

Author(s):

Joseph Y. Abrams ◽

Ryan A. Maddox ◽

Lawrence B. Schonberger ◽

Ermias D. Belay

Keyword(s):

The United States ◽

Annual Number ◽

Considerable Proportion ◽

Term Outcome ◽

Term Survival ◽

Long Term Outcome ◽

History Of ◽

Jakob Disease ◽

Sporadic Cjd

Background/Aims: To assess the frequency and characteristics of intracranial procedures (ICPs) performed and the number of US residents living with a history of ICP. These data are used to calculate the expected annual number of sporadic Creutzfeldt-Jakob disease (CJD) cases among US residents with a history of ICP. Methods: The Nationwide Inpatient Sample provided data on the frequency and types of ICPs, and data from the National Center for Health Statistics was used to produce age-adjusted mortality rates. A model was constructed, which estimated long-term survival and sporadic CJD rates among ICP patients based on procedure type and age. Results: There were an estimated 2,070,488 ICPs in the United States from 1998 to 2007, an average of over 200,000 per year. There were an estimated 2,023,726 US residents in 2013 with a history of ICP in the previous 30 years. In 2013, there was expected to be 4.1 sporadic CJD cases (95% CI 1-8) among people with a history of ICP in the past 30 years. Conclusions: The considerable proportion of US residents living with a history of ICP is important information for retrospective assessments of CJD or any other suspected long-term outcome of ICPs.

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Inflammatory Cerebrospinal Fluid in Sporadic Creutzfeldt-Jakob Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100009422 ◽

2008 ◽

Vol 35 (5) ◽

pp. 625-629

Author(s):

Esther Bui ◽

Eric Ehrensperger ◽

Demetrios J. Sahlas ◽

Brian J. Murray ◽

Catherine Bergeron ◽

...

Keyword(s):

Immune Response ◽

Cerebrospinal Fluid ◽

Transmissible Spongiform Encephalopathy ◽

Underlying Mechanism ◽

Spongiform Encephalopathy ◽

Progressive Dementia ◽

Jakob Disease ◽

Csf Pleocytosis ◽

Inflammatory Profile ◽

Sporadic Cjd

Background:Sporadic Creutzfeldt-Jakob disease (CJD) is a fatal, transmissible spongiform encephalopathy characterized by rapidly progressive dementia, myoclonus, ataxia and akinetic mutism. The underlying mechanism is believed to be a conformational change of a native prion protein which characteristically fails to provoke an immune response. Commensurate with the latter, cerebrospinal fluid (CSF) classically exhibits a non-inflammatory profile.Cases:We report two patients with pathologically-proven sporadic CJD presenting with a significant CSF pleocytosis.Conclusion:Although uncommon, the presence of an inflammatory CSF profile should not exclude the diagnosis of sporadic CJD.

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The importance of recognizing faciobrachial dystonic seizures in rapidly progressive dementias

Dementia & Neuropsychologia ◽

10.1590/s1980-5764-2016dn1004016 ◽

2016 ◽

Vol 10 (4) ◽

pp. 351-357 ◽

Cited By ~ 2

Author(s):

Mateus Mistieri Simabukuro ◽

Paulo Ribeiro Nóbrega ◽

Milena Pitombeira ◽

Wagner Cid Palmeira Cavalcante ◽

Ronnyson Susano Grativvol ◽

...

Keyword(s):

Limbic Encephalitis ◽

Neuropsychiatric Symptoms ◽

Neuronal Cell ◽

Autoimmune Encephalitis ◽

Sao Paulo ◽

São Paulo ◽

Progressive Dementia ◽

Jakob Disease ◽

Rapid Cognitive Decline

ABSTRACT Background: Creutzfeldt-Jakob Disease (CJD) is the prototypical cause of rapidly progressive dementia (RPD). Nonetheless, efforts to exclude reversible causes of RPD that mimic prion disease are imperative. The recent expanding characterization of neurological syndromes associated with antibodies directed against neuronal cell surface or sympathic antigens, namely autoimmune encephalitis is shifting paradigms in neurology. Such antigens are well known proteins and receptors involved in synaptic transmission. Their dysfunction results in neuropsychiatric symptoms, psychosis, seizures, movement disorders and RPD. Faciobrachial dystonic seizure (FBDS) is a novel characterized type of seizure, specific for anti-LGI1 encephalitis. Objective: In order to improve clinical recognition we report the cases of two Brazilian patients who presented with characteristic FDBS (illustrated by videos) and anti-LGI1 encephalitis. Methods: We have included all patients with FBDS and confirmed anti-LGI1 encephalitis and video records of FDBS in two tertiary Brazilian centers: Department of Neurology of Hospital das Clínicas, Sao Paulo University, Sao Paulo, Brazil and Hospital Geral de Fortaleza, Fortaleza, Brazil between January 1, 2011 and December 31, 2015. Results: Both patients presented with clinical features of limbic encephalitis associated with FBDS, hyponatremia and normal CSF. None of them presented with tumor and both showed a good response after immunotherapy. Conclusion: FBDSs may be confounded with myoclonus and occurs simultaneously with rapid cognitive decline. Unawareness of FDBS may induce to misdiagnosing a treatable cause of RPD as CJD.

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SPORADIC CREUTZFELDT-JAKOB DISEASE: A CLINICAL APPROACH OF A SMALL CASE SERIES AND LITERATURE REVIEW

Romanian Journal of Neurology ◽

10.37897/rjn.2017.3.5 ◽

2017 ◽

Vol 16 (3) ◽

pp. 109-115

Author(s):

Sebastian Andone ◽

◽

Sanda Petrutiu ◽

Zoltan Bajko ◽

Anca Motataianu ◽

...

Keyword(s):

Differential Diagnosis ◽

Case Series ◽

Neuronal Loss ◽

Cerebral Atrophy ◽

Clinical Approach ◽

Diagnostic Challenge ◽

Progressive Dementia ◽

Alternative Diagnosis ◽

Extrapyramidal Signs ◽

Jakob Disease

Introduction. Creutzfeldt-Jakob Disease (CJD) is a very rare neurodegenerative disease with no cure that always leads to death. It is the most frequent prion disease and has multiple recognized forms, from which the sporadic form (sCJD) is the most common. The defining histological characteristic of CJD is the accumulation of the abnormal prion protein (PrPSc) along with neuronal loss and spongiform vacuolation. Typical neurological signs found in sCJD are rapidly progressive dementia, myoclonus, visual disturbances, pyramidal signs, extrapyramidal signs, behavioral changes and akinetic mutism. Material and method. We performed a retrospective study over the 2007-2017 period that included five cases of patients diagnosed with probable sCJD from our department. Results. The most common findings in the patients’ MRI were cerebral atrophy and ventricular enlargement, but we also found typical MRI changes such as increased T2 and FLAIR signal intensity in the head of the caudate nucleus, putamen and cerebral cortex. Repeated electroencephalograms showed typical sCJD patterns like periodic sharp wave complexes, mostly with biphasic or triphasic aspect. A complex differential diagnosis and numerous routine investigations (CBC, biochemical analysis, autoimmune panel, HIV antibodies, VDRL, anti-Borrelia antibodies, anti-TPO antibodies, anti-neuronal antibodies, B12 vitamin) were performed, without indicating an alternative diagnosis. All the patients died several months after the onset of symptoms. Conclusions. Given the rarity of the disease and the broad differential diagnosis, CJD proves to be a diagnostic challenge. In the absence of an alternative diagnosis, the association of rapidly progressive dementia, myoclonus, visual and cerebellar signs are highly suggestive for sCJD.

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In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease

Neurology ◽

10.1212/wnl.0000000000005064 ◽

2018 ◽

Vol 90 (10) ◽

pp. e896-e906 ◽

Cited By ~ 12

Author(s):

Gregory S. Day ◽

Brian A. Gordon ◽

Richard J. Perrin ◽

Nigel J. Cairns ◽

Helen Beaumont ◽

...

Keyword(s):

Clinical Diagnosis ◽

Standardized Uptake Value ◽

Progressive Dementia ◽

Pet Tracer ◽

Jakob Disease ◽

Tau Pet ◽

Magnetic Resonance Brain Imaging ◽

Sporadic Cjd

ObjectiveTo determine whether specific patterns of [18F]-AV-1451 tau-PET retention are observed in patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD).MethodsIn vivo [18F]-AV-1451 PET neuroimaging was performed in 5 patients with sporadic CJD (median age, 66 years [63–74]), and results were compared to cognitively normal (CN) persons (n = 44; median age, 68 years [63–74]) and to participants with very mild Alzheimer disease (AD) dementia (n = 8; median age, 77 years [63–90]). Autopsy was completed in all patients with CJD, confirming the clinical diagnosis and permitting characterization of AD neuropathologic change (ADNC).ResultsAll patients with CJD presented with rapidly progressive dementia, typical magnetic resonance brain imaging changes, and elevated CSF total tau (median = 6,519; range = 1,528–13,240 pg/mL). Death occurred within 9 months of symptom onset, with a median 1 month (0.2–3.3) interval from [18F]-AV-1451 PET to autopsy. No unique pattern of [18F]-AV-1451 retention was observed on visual inspection. Summary standardized uptake value ratios in patients with CJD (1.17, 1.08–1.36) were indistinguishable from CN persons (1.14, 0.84–1.54; p = 0.6), and well below those of participants with AD (2.23, 1.60–3.04; p ≤ 0.01). [18F]-AV-1451 retention in patients with CJD and CN persons was similar in brain areas frequently affected in AD and CJD. Neuropathologic analysis confirmed the clinical diagnosis in all patients with CJD. Four patients with CJD also had low-level ADNC (A1B1C0); one patient had intermediate-level ADNC (A2B2C1/2).ConclusionIncreased [18F]-AV-1451 retention was not observed in patients with rapidly progressive dementia due to sporadic CJD. The [18F]-AV-1451 PET tracer maintains good specificity for paired helical tau filaments associated with AD dementia.

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What’s Different about Teratoma-Associated LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series

10.21203/rs.3.rs-30711/v1 ◽

2020 ◽

Author(s):

Cun Li ◽

Hong-bin Cai ◽

Xu Zhao ◽

Xin-cong Xi ◽

Qing Zhou ◽

...

Keyword(s):

Cognitive Deficit ◽

Psychiatric Symptoms ◽

Age At Onset ◽

Thyroid Tissue ◽

Case Series ◽

Pathological Examination ◽

Progressive Dementia ◽

Magnetic Resonance Imaging Mri ◽

Chronic Anxiety

Abstract Background Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. The aim of this study is to report a case of teratoma-associated LGI1 encephalitis, to summarize a retrospective series of LGI1 encephalitis and compare them. Methods Clinical data for 10 people with LGI1 encephalitis were collected. Patients were divided into those with and without associated teratoma, and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical (IHC) assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. Results The LGl1 patient with teratoma was similar to the non-teratoma (NT) group in many ways: age at onset (average 47.3 in NT group); percent presenting with rapidly progressive dementia (RPD) (67% of NT group) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (MRI) (44%); diffuse slow waves on electroencephalography (EEG) (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the NT group. Teratoma pathology was characterized by mostly thyroid tissue and IHC assay confirmed positive LGI1 expression. Conclusion In our series, LGI1 encephalitis included common clinical features: RPD, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, T2-MRI hyperintensity of hippocampus and residual cognitive deficit. We observed some differences in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

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