Rapid Progressive Dementia Research Articles

Clinical Correlates of Cerebrospinal Fluid 14-3-3 Protein in Non-Prion Rapid Progressive Dementia.

The 14-3-3 protein in cerebrospinal fluid (CSF) is a suitable biomarker for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, it has also been detected in various non-prion-related rapidly progressive dementia (RPD), which affected its diagnostic performance and clinical utilization. To investigate the general disease distribution with positive 14-3-3 result and to evaluate the association between CSF 14-3-3 protein and the clinical features in patients with non-prion RPD. A total of 150 patients with non-prion RPD were enrolled. The clinical data were collected and CSF 14-3-3 test was performed for all patients. The distribution of various diseases with a positive 14-3-3 result was analyzed and the association of CSF 14-3-3 with clinical features was tested. The CSF 14-3-3 protein was detected in 23.3% of non-prion RPD patients, and the most frequent diagnoses were autoimmune encephalitis (22.9%) and neurodegenerative disease (22.9%). CSF 14-3-3 protein was more common in older patients (p = 0.028) and those presenting myoclonus (p = 0.008). In subgroup analysis, the positive 14-3-3 test was more common in neurodegenerative disease with a long time from the symptom onset to CSF 14-3-3 test (p = 0.014). CSF 14-3-3 protein could be detected in a broad spectrum of non-prion RPD. In particular, patients with autoimmune encephalitis and rapidly progressive neurodegenerative diseases and those with myoclonus have a greater likelihood of a positive 14-3-3 result. These results could help clinicians interpret the results of CSF 14-3-3 protein more reasonably.

Sporadic Creutzfeldt-Jakob Disease in a Patient With Multiple Sclerosis: A Case Report

Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition and a human prion disease. Rapid progressive dementia, myoclonus, visual disturbances, cerebellar signs, and pyramidal/extrapyramidal symptoms are observed in such patients. However, these are non-specific symptoms and can manifest in a variety of other conditions. The occurrence of sporadic CJD in a patient with multiple sclerosis (MS) is rare. This is the case of a 54-year-old man on natazulimab for MS who developed rapid neurocognitive changes along with visual changes, imbalance issues, and mood changes. Diagnosis of sporadic CJD (sCJD) was confirmed through clinical features, physical examination and electroencephalogram findings, cerebral spinal fluid analysis, and later magnetic resonance imaging findings. sCJD with MS being a rare phenomenon, its recognition requires a high index of suspicion, careful chronological evaluation of the patient’s symptoms, and relevant investigations that can aid in reaching the diagnosis.

Long-term Neuropsychiatric Complications and 18F-FDG-PET Hypometabolism in the Brain From Prolonged Infection of COVID-19.

It is becoming increasingly clear that the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 will have long-term negative consequences. Some patients report functional complaints long after recovery from coronavirus disease-2019 (COVID-19), which include fatigue, breathlessness, heart palpitations, loss or alteration of taste and smell, and problems with attention, memory, and cognition. However, the long-term complications for those patients who had severe symptoms and prolonged hypoxia during their course of their hospital stay is still unknown. We report 2 patients with confirmed diagnoses of COVID-19 who experienced prolonged infection and developed rapid progressive dementia following COVID-19 pneumonia after a follow-up period of 5 to 10 months. As these cases may become more prevalent over time, we should learn to recognize the early signs of long-term COVID-19 complications in those who are especially vulnerable to neurocognitive decline.

Cerebral amyloid angiopathy-related inflammation: current status and future implications.

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

Demencia rápidamente progresiva, sobre el reporte de un caso de Creutzfeldt-Jakob

The Creutzfeldt-Jakob disease is a neurodegenerative, neuroselective and fatal entity, that is not usually reported in Mexico. We present a 40-year-old male patient who presents the onset of this illness, with short-term memory disorder, depressive episodes and emotional lability with a tendency to irritability. He also presents space disorientation, decreased strength of the left and lateral hemibody drive in the ipsilateral walk, and insomnia, for which he is admitted to the hospital during 40 days for diagnostic approach. Several studies were carried out during his hospital stay, the most relevant for the diagnosis: a magnetic resonance which presented ""cortical ribboning"" and hyperintensities in the nuclei of the base, both diagnosis highly suggested the pathology. The positive results to protein 14-3-3 reaffirmed the diagnosis. After 15 months of the onset of neurological symptoms, the patient presented symptoms of pneumonia, which lead to the hospitalization. During his stay, he presented a pulmonary abscess and rapid progressive dementia. The patient died in the hospital by a pulmonary sepsis 18 months after the onset of symptoms. No necropsy was performed, following the current standards for the disease management. Keywords: Creutzfeldt-Jakob disease; prion diseases; rapidly progressive dementia.

Neuropathology of Cerebellar Cortical Atrophy

Cerebellar cortical atrophy (CCA) is a neurodegenerative disease characterized by the loss of Purkinje cells, frequently associated with atrophy of the inferior olivary nucleus. The diagnosis of CCA requires a pathologic assessment; however, this term has also been used in clinical practice as a diagnosis of exclusion for sporadic, adult-onset, and progressive ataxia. For the clinical diagnosis of CCA, diagnostic criteria for idiopathic cerebellar ataxia (IDCA) have been proposed. We herein describe two patients with a pathologic diagnosis of CCA. The first patient was clinically suspected to have Creutzfeldt-Jakob disease due to rapid progressive dementia and ataxia. The second patient was clinically diagnosed with progressive supranuclear palsy based on imbalance, frequent falls, and vertical gaze palsy. The se cases suggest that the clinical presentation of CCA is heterogeneous, and CCA does not always meet the criteria for IDCA. Therefore, the term CCA should be used solely for a pathologic diagnosis.

Anti-dipeptidyl-peptidase-like protein 6 encephalitis, a rare cause of reversible rapid progressive dementia and insomnia

Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare type of autoimmune encephalitis. We present a case of a 72-year-old male with anti-DPPX encephalitis who developed rapidly progressive cognitive decline, psychiatric and sleep problems, severe abdominal pain and diarrhea. Antibodies against DPPX were positive both in serum and cerebrospinal fluid. 18F-FDG PET-MR imaging indicated hypometabolism in the bilateral temporal lobes and thalamus. No related tumors were found, and the patient responded to immunotherapy without relapse at the 3-year follow-up. The present case enriches the understanding of the clinical, imaging manifestations and prognosis of anti-DPPX encephalitis.

Identification of a rare presenilin 1 single amino acid deletion mutation (F175del) with unusual amyloid-β processing effects

We report the novel presenilin 1 (PSEN1) single amino acid deletion mutation F175del. Comprehensive clinical work-up, including cerebral MRI, FDG-PET, and CSF analysis, was performed in a male who had developed forgetfulness at the age of 39. Alzheimer’s disease dementia was diagnosed according to established criteria. The index patient manifested rapid progressive dementia, seizures, and myoclonus, and a Pisa syndrome as a side effect of donepezil treatment. The PSEN1 mutation F175del was found on genetic testing. It was rendered very likely pathogenic as amyloid-β (Aβ) peptide 42 was elevated in a cell culture model compared to presenilin 1 wild-type controls. An additional, unusual increase in Aβ39 indicates a rarely observed product line deviation in the generation of the shorter Aβ species. Our observations extend the range of PSEN1 mutations to be considered in familial dementia. We demonstrate that deletion of a single conserved amino acid, which is very rare compared to missense mutations as the common cause for PSEN1-associated Alzheimer’s disease, can lead to an unusual profile of Aβ species.

Update on PET in neurodegenerative and neuroinflammatory disorders manifesting on a behavioural level: imaging for differential diagnosis

To give an update on recent findings concerning the use of PET for differential diagnosis in neurodegenerative and neuroinflammatory disorders manifesting on a behavioural level. Although accurate differential diagnosis of dementia can be achieved by imaging disease-specific patterns of cerebral glucose metabolism with [F]fluorodeoxyglucose ([F]FDG)-PET, the diagnostic impact of [F]FDG-PET in primary psychiatric disorders is limited. Amyloid-beta PET provides an incremental value beyond [F]FDG-PET in the differential diagnosis of dementia and was proposed as a biomarker defining the so-called Alzheimer continuum. Recently developed tau-specific tracers might also aid in the diagnostic process (biological definition of Alzheimer's disease together with amyloid-beta). Surpassing the diagnostic accuracy of other techniques, such as MRI, [F]FDG-PET has also gained widespread clinical use for diagnosis and follow-up of paraneoplastic and autoimmune disorders of the central nervous system (CNS) as an important differential diagnosis for rapid progressive dementia and subacute onset of psychiatric syndromes. Molecular neuroimaging with PET is an established method for the differential diagnosis of neurodegenerative and autoimmune CNS disorders manifesting on a behavioural level with significant therapeutic and prognostic impact. Future prospective studies are needed to define the value of tau imaging for diagnosis and prognosis in neurodegenerative disorders.

Probable Creutzfeldt-Jakob disease\u2014a case report at Suez Canal University Hospital, Egypt

IntroductionAmong transmissible spongiform encephalopathies, Creuzfeldt-Jakob disease is considered a rare neurodegenerative disorder. The clinical features include rapid progressive dementia and myoclonic jerks, which progresses to death.Case descriptionWe report a case of a 65-year-old man, with progressive gait instability and impaired cognition with normal brain MRI. After 1 week, his symptoms became worse, EEG showed periodic sharp wave complexes, suggestive of Creuzfeldt-Jakob disease, and CSF was normal. One week later, he developed bradyphrenia and myoclonic fits. Brain MRI showed hyper-intensities mainly in the right frontal and occipital cortical gyri and caudate areas. After a few days, the patient developed akinetic mutism intractable fits, was admitted to the ICU, and was deceased after a few days.Discussion and evaluationBased on the 2010 CDC Criteria, our case was diagnosed as probable sporadic Creutzfeldt-Jakob disease (sCJD). The main findings were rapidly progressive dementia, ataxia, akinetic mutism, and myoclonus. EEG and MRI findings support the diagnosis.ConclusionsOur case showed clinical, electrophysiological, and radiological features typical of probable sCJD—a rare, incurable, and fatal disease.

Antibody-LGI 1 autoimmune encephalitis manifesting as rapidly progressive dementia and hyponatremia: a case report and literature review

BackgroundAnti leucine-rich glioma inactivated 1 (LGI1) encephalitis is a rare autoimmune encephalitis (AE), characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, psychiatric disturbances and hyponatremia. Antibody-LGI 1 autoimmune encephalitis (anti-LGI1 AE) has increasingly been recognized as a primary autoimmune disorder with favorable prognosis and response to treatment.Case presentationHerein, we reported a male patient presenting as rapidly progressive dementia and hyponatremia. He had antibodies targeting LGI1 both in the cerebrospinal fluid and serum, which demonstrated the diagnosis of typical anti-LGI1 AE. The scores of Mini-Mental State Examination and Montreal Cognitive Assessment were 19/30 and 15/30, respectively. Cranial magnetic resonance images indicated hyperintensities in bilateral hippocampus. The findings of brain arterial spin labeling and Fluorine-18-fluorodeoxyglucose positron emission tomography showed no abnormal perfusion/metabolism. After the combined treatment of intravenous immunoglobulin and glucocorticoid, the patient’s clinical symptoms improved obviously.ConclusionsThis case raises the awareness that a rapid progressive dementia with predominant memory deficits could be induced by immunoreactions against LGI1. The better recognition will be great importance for the early diagnosis, essential treatment, even a better prognosis.

Genetic Creutzfeldt-Jakob disease with a glutamate-to-lysine substitution at codon 219 (E219K) in the presence of the E200K mutation presenting with rapid progressive dementia following slowly progressive clinical course

A 57-year-old man developed rapidly progressive dementia and a gait disturbance over 4 months. The patient had a slowly progressive executive dysfunction and speech problems for 4 years and was previously monitored in our outpatient clinic following a diagnosis of frontotemporal dementia. Diffusion-weighted MRI revealed high signal intensities in the right caudate nucleus and the bilateral cortices. Cerebrospinal fluid analysis showed increased levels of the 14-3-3 and total tau proteins. Periodic synchronous discharge was not evident on an electroencephalogram. Prion protein gene analysis identified a glutamate-to-lysine substitution at codon 219 (E219K) in the presence of the E200K mutation, leading to a genetic diagnosis of genetic Creutzfeldt-Jakob disease (CJD). The E219K polymorphism found on the allele of the E200K mutation may have influenced the characteristic clinical course of our patient that differed from that of typical E200K genetic CJD.

Report and literature review on two cases with different kinds of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD), also known as corticostriate spinal degeneration, subacute spongiform encephalopathy or infectious spongiform encephalopathy, is a type of degenerative disease of the central nervous system caused by prion protein (PrP) infection, which is the most common type of human PrP disease. CJD is genetic and infectious, and is one of the most common causes of rapid progressive dementia with rare clinical occurrence. Herein, we report the clinical conditions of 2 cases of patients with different type of CJD we treated and followed up recently, and a review of relevant literature. The patient in case 1 was admitted due to ‘dizziness with hypomnesis, and mental and behavior disorder’. He was considered to suffer from a central nervous system infection - a viral encephalitis, but one month later, a repeated cranial MRI showed lace sign of bilateral frontotemporal parietal lobe in DWI sequence, an AEEG indicated periodic synchronous discharge, and the detection of cerebrospinal fluid 14-3-3 protein was positive. It was suggested to be diagnosed as the sporadic CJD. The patient in case 2 was admitted because of ‘progressive hypomnesis’. Cerebrospinal fluid 14-3-3 protein detection was negative, but the V203I-related mutation was found in the PRNP gene detection. The patient was suggested to be diagnosed as genetic CJD. Both patients died in a short time. An earlier diagnosis can provide a time window for treatment, and avoid unnecessary transmission in hospital, as well as doctor-patient dispute.

Bilaterales hippocampales primäres ZNS-Lymphom: ungewöhnliche Differentialdiagnose eines rasch progredienten dementiellen Syndroms

We report on a 63-year old man suffering from rapid progressive dementia due to bilateral hippocampal primary CNS lymphoma. Early diagnosis especially in secondary dementia is essential because of potentially treatable aetiologies with regression of cognitive and behaviour abnormalities. Characteristic imaging findings especially in inflammatory and neoplastic lesions affecting the hippocampal structures are discussed.

Dural Arteriovenous Fistula Manifested as Rapid Progressive Dementia Successfully Treated by Endovascular Embolization Only.

A 43-year-old male presented with daytime sleepiness at work and indifferent behavior like never before. Two weeks prior to hospital admission, he had episodic memory loss with well preserved remote memory. Brain MRI showed a dural arteriovenous fistula (DAVF) in the right lateral transverse sinus with a bilateral thalamic venous infarction. Cerebral angiography confirmed a right transverse sigmoid dural arteriovenous fistula with a feeding artery of the right occipital artery and left posterior meningeal artery. The DAVF was completely eliminated through multiple endovascular interventions. Recently, endovascular treatment has become one of the main therapeutic options to obliterate a fistulous site, which has led to a rapid diagnostic approach and management of DAVFs with high curative rates. We report a rare case of posterior fossa located at a dural arteriovenous fistula that caused rapid progressive dementia and was successfully eliminated through only endovascular treatment.

Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features.

Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments.Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles.Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms.Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.

Sry‐like high‐mobility group box antibody‐related paraneoplastic cerebellar degeneration in the background of underlying non‐small cell lung cancer

AbstractBackgroundParaneoplastic neurological syndromes (PNS) are defined as all non‐metastatic neurological complications of cancer in which no other etiologies, such as vascular, infectious or metabolic, were determined. Recently, Sry‐like high‐mobility group box (SOX1) antibody associated with PNS has been described, and is associated with Lambert–Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration and paraneoplastic peripheral neuropathy invariably in the background of underlying small‐cell lung cancer.Case presentationA 75‐year‐old man was admitted to our neurology clinic at Hacettepe University Hospital, Sihhiye, Ankara, Turkey with complaints of imbalance and memory impairment that had started 2 months earlier and progressively increased. Neurological examination showed a state of delirium in the background of rapid progressive dementia and severely truncal ataxia. Cranial magnetic resonance imaging was unremarkable; however, in further investigations, thoracic tomography yielded bilateral hilar lymphadenopathy, and paraneoplastic antibody investigations resulted in positive SOX1 antibody. The following thoracic excisional lymph node biopsy investigations supported the diagnosis of non‐small‐cell lung cancer and paraneoplastic cerebellar degeneration associated with SOX1 antibody in the background of non‐small‐cell lung cancer. Adjuvant chemotherapy was started, but the patient deteriorated, which prevented proper plasmapheresis therapy. He died in the second month of admission as a result of severe sepsis leading to septic shock.ConclusionsHere, we show the second case diagnosed with PNS in association with non‐small‐cell lung cancer. We note the importance of SOX1 antibody as a marker for PNS, and suggest that investigations of this antibody be carried out in larger case studies.

Tumor primário de pulmão simulando doença de Alzheimer: relato de caso

RESUMO Retratamos o relato de um homem de 61 anos que apresentava um glioblastoma multiforme em região do giro têmporo-occipital lateral esquerdo que rechaça cranialmente o hipocampo e o corno temporal do ventrículo lateral correspondente. Não havia sinais e sintomas neurológicos e o quadro clínico lembrava a demência de Alzheimer. Havia comprometimento de memória e alterações comportamentais com duração de três meses. Foram afastadas inicialmente outras causas de demência rapidamente progressivas e a ressonância magnética revelou a etiologia tumoral dos sintomas neuropsiquiátricos. Foi submetido à bateria de testes neuropsicométricos com pontuação compatível com doença de Alzheimer (DA). Em razão de extensa área de edema, foi introduzida dexametasona com reversão completa dos sintomas neuropsiquiátricos iniciais e a repetição da bateria neuropsicológica mostrou melhora acentuada em todos os testes. Optou-se por tratamento conservador, após biópsia por agulha, com evolução para óbito em cinco meses.

Clinical and neuropathological features of rapid progressive Dementia with Lewy Bodies

Objectives: Dementia with Lewy Bodies (DLB) can follow a very rapid progressive disease course, resembling Creutzfeldt-Jakob’s Disease (CJD)1. This is the first study to describe the neuropathological findings in a cohort of rapid progressive DLB patients. Our aim is to test whether the presence and load of Lewy Bodies and concomitant pathology differs between rapid progressive DLB and classical DLB.

Clinical and neuropathological features of rapid progressive dementia with Lewy Bodies

Clinical and neuropathological features of rapid progressive dementia with Lewy Bodies