RESUMEN

Sporadic Creutzfeldt-Jakob disease (SCJD) is a rare neurodegenerative disease with a very low prevalence. The aetiology is theorised to be genetic. Modern laboratory techniques, such as the real-time quaking-induced conversion (RT-QuIC) assay, have allowed us to diagnose CJD with greater sensitivity and specificity. Previously, the diagnosis rested primarily on a post-mortem brain biopsy. Although advancements in laboratory techniques have allowed earlier diagnosis of CJD, the treatment is still supportive. Research is still ongoing for a curative treatment, but so far, the fatality rate remains at 100%. Early vague symptoms of CJD delay the diagnosis further, as multiple pathologies need to be ruled out before consideration of the diagnosis of CJD. This case report describes a similar case of sporadic CJD diagnosed in an otherwise fit and well patient.

RESUMEN

BACKGROUND: Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease (CJD), particularly in patients with acquired immune deficiency syndrome (AIDS). CASE SUMMARY: We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure. The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins. His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern. Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination. Initially, symptomatic treatment and administration of amantadine were pursued for presumed CJD, but the patient's condition continued to deteriorate. By contrast, the patient's condition improved following anti-HIV therapy. This individual is also the only patient with this prognosis to have survived over 4 years. Thus, the diagnosis was revised to HAD. CONCLUSION: In the diagnostic process of rapidly progressive dementia, it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty. The 14-3-3 protein should not be regarded as the definitive marker for CJD. Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision, especially in AIDS patients with potential CJD. Ultimately, a trial of diagnostic treatment may be considered when additional testing is not feasible.

RESUMEN

Variably protease-sensitive prionopathy (VPSPr) is a recently characterised rare subtype of sporadic prion disease, mainly affecting individuals with valine homozygosity at codon 129 in the prion protein gene, with only seven methionine homozygote cases reported to date. This case presents clinical, neuropathological and biochemical features of the eighth VPSPr case worldwide with methionine homozygosity at codon 129 and compares the features with the formerly presented cases.The patient, a woman in her 70s, presented with cognitive decline, impaired balance and frequent falls. Medical history and clinical presentation were suggestive of a rapidly progressive dementia disorder. MRI showed bilateral thalamic hyperintensity. Cerebrospinal fluid real-time quaking-induced conversion was negative, and the electroencephalogram was unremarkable. The diagnosis was established through post-mortem pathological examinations. VPSPr should be suspected in rapidly progressive dementia lacking typical features or paraclinical results of protein misfolding diseases.

Asunto(s)

RESUMEN

A previously healthy man in his 80s was admitted to a district general hospital with rapidly progressing dementia, gait abnormalities and myoclonus alongside COVID-19 infection. Investigations showed mild elevation of C-reactive protein and neutrophils, unremarkable CT head and mildly raised protein in cerebrospinal spinal fluid (CSF). Brain MRI revealed bilateral cortical and striatal diffusion restriction and electroencephalogram (EEG) findings showed diffuse activity slowing with high amplitude sharp/slow-wave complexes. He was diagnosed with probable sporadic Creutzfeldt-Jakob disease (CJD) and management prioritised comfort and care. He passed away two weeks following admission and a mere 8 weeks after the first onset of symptoms.We present the first documented case of probable CJD with concomitant COVID-19 infection in the UK. We identified six other cases worldwide identified in our literature review. These cases suggest a role of COVID-19 in the rapid progression of CJD and add to the growing evidence of its neuroinflammatory role in other forms of neurodegenerative diseases.

Asunto(s)

RESUMEN

Prion diseases are rare neurodegenerative diseases that have a rapid evolution. Creutzfeldt-Jakob disease (CJD) is the most common and its sporadic form the most frequent. Definitive diagnosis is only obtained through autopsy, and there are currently no available treatments. Here, we present a case of an 84-year-old woman presenting with resting tremor, abnormal gait, frequent falls, apraxia, visual hallucinations, and delirium. There were no signs of relevant metabolic, infectious, or nutritional alterations, and brain computed tomography (CT) scan and magnetic resonance imaging (MRI) had no significant findings. Two months later, the patient was completely immobile with mutism, seizures, and myoclonus. In the presence of a rapidly progressive dementia associated with myoclonus, it was hypothesized that the patient had CJD. The patient's clinical state deteriorated, she died, and autopsy confirmed sporadic CJD. The purpose of this case is to highlight a rare disease that can go undiagnosed because of low awareness and clinical suspicion and the importance of the differential diagnosis of dementia, a common disease at this age.

RESUMEN

Methionine/valine polymorphism at position 129 of the human prion protein, huPrP, is tightly associated with the pathogenic phenotype, disease progress, and age of onset of neurodegenerative diseases such as Creutzfeldt-Jakob disease or Fatal Familial Insomnia. This raises the question of whether and how the amino acid type at position 129 influences the structural properties of huPrP, affecting its folding, stability, and amyloid formation behavior. Here, our detailed biophysical characterization of the 129M and 129V variants of recombinant full-length huPrP(23-230) by amyloid formation kinetics, CD spectroscopy, molecular dynamics simulations, and sedimentation velocity analysis reveals differences in their aggregation propensity and oligomer content, leading to deviating pathways for the conversion into amyloid at acidic pH. We determined that the 129M variant exhibits less secondary structure content before amyloid formation and higher resistance to thermal denaturation compared to the 129V variant, whereas the amyloid conformation of both variants shows similar thermal stability. Additionally, our molecular dynamics simulations and rigidity analyses at the atomistic level identify intramolecular interactions responsible for the enhanced monomer stability of the 129M variant, involving more frequent minimum distances between E196 and R156, forming a salt bridge. Removal of the N-terminal half of the 129M full-length variant diminishes its differences compared to the 129V full-length variant and highlights the relevance of the flexible N terminus in huPrP. Taken together, our findings provide insight into structural properties of huPrP and the effects of the amino acid identity at position 129 on amyloid formation behavior.

Asunto(s)

RESUMEN

Alzheimer´s disease is characterized by hyperphosphorylated tau neurofibrillary tangles and beta-amyloid plaques. Both molecules can be easily measured in human fluids or tissue extracts by immunoassays. However, the different molecular weight species can only be differentiated on Western Blot gels. Analysis of native proteins from polyacrylamide gels is also not well characterized. Hence, we developed a modified method to elute proteins or peptides from native agarose gels. Initially, full-length tau (60 kDa) and beta-amyloid(42) (4 kDa) were separated on a Western Blot gel and eluted from native agarose gels (WANGEL) using an elution system inside a polypropylene tube. The eluates were analyzed with the Lumipulse immunoassay. Both molecules were successfully eluted into 1% agarose gels to the cathode and were detected in the eluate. Additionally, tau was eluted from mouse cortical extracts, but was below the detection limit when eluted from human cerebrospinal fluid. Beta-amyloid(40) was eluted from CSF extracts and detected by Lumipulse. In cortical extracts taken from transgenic mice (APP_SweDI) beta-amyloid(42) was detectable as a native peptide and small oligomeric aggregates. Taken together, our novel WANGEL method enables fast, easy and cheap elution of protein/peptides from polyacrylamide/agarose gels with a subsequent analysis by Lumipulse immunoassay. Three bullet points:•Beta-amyloid and tau are major hallmarks in Alzheimer´s disease and are established cerebrospinal fluid biomarkers.•Lumipulse is a method to measure beta-amyloid and tau in cerebrospinal fluid in the pg/mL range.•Western Blot and our novel combined native agarose method (WANGEL) allows an easy and fast determination of the molecular size in combination with Lumipulse.

RESUMEN

We report a case of genetic Creutzfeldt-Jakob disease (gCJD), which has a clinical phenotype that is highly similar to Fatal Family Insomnia (FFI) and has a triad of Wernicke-Korsakoff syndrome (WKs) at the developmental stage of the disease. The 51-year-old male complained of sleep disorder and imbalance who had visited five different hospitals before diagnosed. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk, and memory disturbances. The disturbances increased during the course of the disease, which led to the death of the patient 18 months after the appearance of the signs. Although the patient show negative in brain magnetic resonance imaging (MRI) and 14-3-3 protein of cerebrospinal fluid (CSF), he was finally diagnosed with gCJD disease by the human prion protein (PRNP) gene mutations.

Asunto(s)

RESUMEN

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, fatal, neurodegenerative disease caused by accumulation of abnormally folded prion protein. sCJD can have a long asymptomatic incubation period, with little known about this period. We describe the first-ever participant within the population-based Rotterdam Study diagnosed with sCJD. We retrieved clinical data from both the population-based Rotterdam Study and the National Prion Disease Registry. In 2011, a female participant of the Rotterdam Study was diagnosed with probable sCJD and registered into the Registry. Four months earlier, she was classified as having mild cognitive impairment based on assessment in the Rotterdam Study. Clinical deterioration was rapid, with the patient dying 7 months after the research centre visit. Postmortem brain autopsy confirmed the diagnosis of sCJD. In conclusion, we describe the first case diagnosed with sCJD who during diagnostic workup for sCJD was classified as having mild cognitive impairment in a population-based cohort study.

Asunto(s)

RESUMEN

Neurodegenerative diseases (NDDs) are challenging to understand, diagnose, and treat. Revealing the genomic and transcriptomic changes in NDDs contributes greatly to the understanding of the diseases, their causes, and development. Moreover, it enables more precise genetic diagnosis and novel drug target identification that could potentially treat the diseases or at least ease the symptoms. In this study, we analyzed the transcriptional changes of nuclear-encoded mitochondrial (NEM) genes in eight NDDs to specifically address the association of these genes with the diseases. Previous studies show strong links between defects in NEM genes and neurodegeneration, yet connecting specific genes with NDDs is not well studied. Friedreich's ataxia (FRDA) is an NDD that cannot be treated effectively; therefore, we focused first on FRDA and compared the outcome with seven other NDDs, including Alzheimer's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, frontotemporal dementia, Huntington's disease, multiple sclerosis, and Parkinson's disease. First, weighted correlation network analysis was performed on an FRDA RNA-Seq data set, focusing only on NEM genes. We then carried out differential gene expression analysis and pathway enrichment analysis to pinpoint differentially expressed genes that are potentially associated with one or more of the analyzed NDDs. Our findings propose a strong link between NEM genes and NDDs and suggest that our identified candidate genes can be potentially used as diagnostic markers and therapeutic targets.

RESUMEN

BACKGROUND: Human transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders of short duration. There are few studies on TSE survival. This study sought to analyze the survival and related factors of a TSE patient cohort, based on a nationwide surveillance system in Spain. METHODS: Survival analyses were performed on 1,530 cases diagnosed across the period 1998-2018 in Spain. We calculated median survival times and plotted survival curves using the Kaplan-Meier method for all cases and for sporadic TSE (sTSE) and genetic TSE (gTSE). Crude and adjusted Cox proportional hazard models were used to identify variables associated with shorter survival. FINDINGS: Median age at onset decreased from the sporadic forms to gTSE and, lastly, to acquired TSE. Overall median and interquartile range (IQR) survival time was 5.2 (IQR, 3.0-11.7) months and 4.9 (IQR, 2.8-10.8) months in sporadic cases and 9 (IQR, 4.9 to over 12) months in genetic cases, p < 0.001. Male sex, older age at onset, presence of 14-3-3 protein, typical MRI, and MM and VV polymorphisms at codon 129 were associated with shorter survival. gTSE showed higher survival in crude comparisons but not after adjustment. INTERPRETATION: TSE survival in Spain replicates both the magnitude of that shown and the TSE entity-specific population patterns observed in Western countries but differs from features described in Asian populations, such as the Japanese. The reduction in differences in survival between gTSE and sTSE on adjusting for covariates and international patterns might support the view that gTSE and sTSE share causal and pathophysiological features.

RESUMEN

Creutzfeld-Jakob disease (CJD) is a rare neurodegenerative condition characterized by rapid progression and fatal outcomes. Patients with progressive dementia and associated atypical features should be investigated, especially with the MRI brain for CJD. Cortical ribboning on diffusion-weighted MRI images is a very crucial diagnostic sign for CJD. Here we present a case of a 52-year-old woman admitted to the hospital after a seizure episode and two-month history of altered mental status. She presented with a 40-minute episode of status epilepticus, necessitating admission to the intensive care unit. Head CT showed no acute intracranial abnormalities, and MRI showed generalized brain atrophy. Electroencephalography (EEG) demonstrated an intermittent slowing of the left hemisphere. Two weeks after admission, she got discharged. Four days later, she presented to the hospital after being found disoriented in a park. MRI showed ventricular dilation and a questionable focus of restricted diffusion in the left thalamus posteriorly. CJD protein panel was collected. Three days after discharge, she was brought to the hospital, and CJD protein testing revealed the presence of 14-3-3 protein, elevated T-tau, and negative real-time quaking-induced conversion (RT-QuIC). The National Prion Disease Surveillance Center reviewed her case, and the CJD diagnosis was confirmed.

RESUMEN

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)).

Asunto(s)

RESUMEN

Sporadic Creutzfeldt-Jakob disease is the predominant type of human prion disease. While routine diagnostic in phenotypic cases has advanced considerably, the clinical heterogeneity and rarity of subtypes continue to constitute a major clinical and diagnostic challenge. Here, we report a peculiar case of the Heidenhain-variant of MM1 sporadic Creutzfeldt-Jakob disease presenting as a stroke mimic in an 81-year-old patient with a rapid and clinically distinct course of disease as compared to previously reported cases. While 14-3-3 protein was negative, clinical findings substantiated by 18F-FDG-PET imaging and RT-QuIC-Assay were able to establish the diagnosis. We conclude that in cases presenting with rapid progressive dementia secondary to sudden cortical anopsia the Heidenhain-variant of CJD should be considered.

Asunto(s)

RESUMEN

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare cause of genetic prion disease. Overlapping neurological, cognitive and psychiatric symptoms make GSS difficult to diagnose based on clinical features alone. We present a 40-year-old man without relevant medical or family history who developed progressive neurocognitive and behavioural symptoms over 3 years. Initial extensive diagnostic workup of his variable motor symptoms was unrevealing and he was diagnosed with conversion disorder. This diagnosis persisted for over 2 years, despite progressive neurocognitive symptoms. He eventually developed dementia and severe neurological impairment. Repeat brain MRI revealed generalised cortical volume loss, establishing the diagnosis of a rapidly progressive neurodegenerative process. He ultimately died from aspiration pneumonia at age 43. Postmortem neuropathological examination showed widespread multicentric prion protein amyloid plaques characteristic of GSS. Ultimately, genetic testing of brain tissue revealed a heterozygous A117V variant in the PNRP gene, confirming the diagnosis.

Asunto(s)

RESUMEN

Visual snow is the perception of flickering dots throughout the entire visual field and occurs with other symptoms of dysfunctional central sensory processing. We describe a patient who presented with visual snow, illusory visual motion, photopsia, and reduced night vision. He subsequently developed progressive cognitive impairment, myoclonus and ataxia. A diagnosis of sporadic Creutzfeldt-Jakob Disease was confirmed on post-mortem examination more than 49 months after symptom onset. The visual snow syndrome is typically benign, but our patient illustrates that occasionally it is the first manifestation of a serious brain disease. Careful application of the diagnostic criteria for the visual snow syndrome is important, particularly with the use of neuroimaging to exclude pathology in the occipital cortex.

Asunto(s)

RESUMEN

We report the case of a 78-year-old man who showed a subacute onset of severe cognitive impairment, ataxia, tremor, stimulus sensitive myoclonus and hypophonia. Since a few weeks, he received a treatment with a combination of tricyclic antidepressants for mood disorder. The clinical picture mimicked Creutzfeldt-Jakob disease (CJD), but we could rule out this diagnosis by means of cerebrospinal fluid (CSF) analysis, which showed normal level of tau protein and Aß1-42, being also negative for CSF 14-3-3 protein. A complete clinical recovery was observed after the discontinuation of antidepressants. So far, some cases of drug-induced CJD-like syndrome have been described. In our experience, early CSF analysis shows high diagnostic usefulness in order to exclude CJD.

Asunto(s)

RESUMEN

Fatal familial insomnia (FFI) is a rare prion disease commonly inherited in an autosomal dominant pattern from a mutation in the PRioN Protein (PRNP) gene. Hashimoto's encephalopathy (HE) is characterised by encephalopathy associated with antithyroid peroxidase (TPO) or antithyroglobulin (Tg) antibodies. These two conditions characteristically have differing clinical presentations with dramatically different clinical course and outcomes. Here, we present a case of FFI mimicking HE. A woman in her 50s presented with worsening confusion, hallucinations, tremor and leg jerks. Several maternal relatives had been diagnosed with FFI, but the patient had had negative genetic testing for PRNP. MRI of brain, cervical and thoracic spine were unremarkable except for evidence of prior cervical transverse myelitis. Cerebrospinal fluid analysis was normal. Anti-TPO and anti-Tg antibodies were elevated. She was started on steroids for possible HE and showed improvement in symptoms. Following discharge, the results of her PRNP gene test returned positive for variant p.Asp178Asn.

Asunto(s)

RESUMEN

We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14-3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.

Asunto(s)