Clinical Neuroscience

Additional value of tau protein measurement in the diagnosis of Creutzfeldt-Jakob disease

CSEH Katalin Edina1, VERES Gábor1,2, DANICS Krisztina3,4, SZALÁRDY Levente1, NÁNÁSI Nikolett1, KLIVÉNYI Péter1, VÉCSEI László1,2, ZÁDORI Dénes1

JANUARY 30, 2019

Clinical Neuroscience - 2019;72(01-02)

DOI: https://doi.org/10.18071/isz.72.0039

Since the definite diagnosis of Creutzfeldt-Jakob disease (CJD) can currently only be provided by autopsy, there is a special need for fine diagnostic tools in live patients to achieve accurate diagnosis as early as possible. The aim of this study was to perform a preliminary retrospective analysis on the utility of the measurement of total Tau (tTau) and some other biomarkers from the cerebrospinal fluid (CSF) of patients with rapidly progressive dementia in the diagnostic work up of CJD. Beside the assessment of relevant clinical data and the findings of electroencephalography and brain magnetic resonance imaging, the presence of 14-3-3 protein and the levels of tTau were determined by Western blot technique and enzyme-linked immunosorbent assay from the CSF of 19 patients diagnosed with rapidly progressive dementia between the period of 2004-2017 at the Department of Neurology, University of Szeged. This preliminary study provided 100% sensitivity for 14-3-3, and interestingly, only 40% specificity to support the clinical diagnosis of CJD. Regarding tTau, the sensitivity values were calculated to be 100% or 83%, whereas the specificity values were 71% or 86%, depending on the applied cut-off levels. The poor specificity of 14-3-3 is not in line with literature data and may be the result of the small number of patients in the cohort with non-prion disease, predominantly consisting of disorders with considerable tissue damage, whereas tTau presented good sensitivity and specificity values. The combined application of these and novel chemical biomarkers may increase both sensitivity and specificity to a desired level.

AFFILIATIONS

  1. Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged
  2. MTA-SZTE Neuroscience Research Group, Szeged
  3. Prion Disease and Neuropathology Reference Center, Semmelweis University, Budapest
  4. Department of Forensic and Insurance Medicine, Semmelweis University, Budapest

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

[Tension type headache and its treatment possibilities]

ERTSEY Csaba, MAGYAR Máté, GYÜRE Tamás, BALOGH Eszter, BOZSIK György

[Tension type headache, the most common type of primary headaches, affects approximately 80% of the population. Mainly because of its high prevalence, the socio-economic consequences of tension type headache are significant. The pain in tension type headache is usually bilateral, mild to moderate, is of a pressing or tightening quality, and is not accompanied by other symptoms. Patients with frequent or daily occurrence of tension type headache may experience significant distress because of the condition. The two main therapeutic avenues of tension type headache are acute and prophylactic treatment. Simple or combined analgesics are the mainstay of acute treatment. Prophylactic treatment is needed in case of attacks that are frequent and/or difficult to treat. The first drugs of choice as preventatives of tension type headache are tricyclic antidepressants, with a special focus on amitriptyline, the efficacy of which having been documented in multiple double-blind, placebo-controlled studies. Among other antidepressants, the efficacy of mirtazapine and venlafaxine has been documented. There is weaker evidence about the efficacy of gabapentine, topiramate, and tizanidin. Non-pharmacological prophylactic methods of tension type headache with a documented efficacy include certain types of psychotherapy and acupuncture. ]

Clinical Neuroscience

Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in essential tremor

TAK Zeynal Abidin Ali, SENGUL Yildizhan

Introduction - Although essential tremor (ET) is the most common cause of tremor, the pathology and underlying mechanisms have not fully understood yet. In addition to kinetic tremor, patients may present several types of tremor, gait ataxia, hearing deficits and eye movement abnormalities. Non-motor symptoms and signs have also added to definition of ET. There is significant evidence indicating the neurodegenerative nature of the disease. New studies indicate that inflammation may have a place in the etiology. The neutrophil-to lymphocyte ratio (NLR) and the platelet-to lymphocyte ratio (PLR) have recently begun to be used as a marker of systemic inflammation. Our study aims at finding a clue for systemic inflammation in ET. Methods - 67 patients with ET and 40 healthy controls were recruited for the study. The total white blood cells (WBC), absolute neutrophil count, lymphocyte count and platelet count were retrieved. The NLR was calculated by dividing the neutrophil count by the lymphocyte count and the PLR was calculated by dividing the platelet count by the lymphocyte count. Results - Patient and control groups were similar in terms of age and gender. The mean age of patient group was 25.29 ± 8.24 years and that of control group was 26.77 ± 6.73 years. The NLRs were 1.85 ± 0.58 in the patient group and 1.96 ± 0.53 in the control group. For the patient group and the control group the PLRs were 103.52 ±32.80 and 91.26 ± 31.57 respectively. There were no statistically significant differences between the participants for both NLR and PLR. Conclusion - The pathophysiological mechanism for essential tremor (ET) remains unclear. However, there is an increasing amount of research being conducted on the subject. Discussions about ET’s definition as a neurodegenerative disease are ongoing. Although previous studies showed that neuroinflammation could be a part of etiology of disease, this study has failed to demonstrate systemic inflammation in ET.

Clinical Neuroscience

Axillary mononeuropathy after herpes zoster infection misdiagnosed as neuropathic pain

GÜL Sinem Sidika, AKARSU Oguz Emel

Zoster-associated extremity paresis is a rare complication of herpes zoster (HZ) and is usually due to zoster-associated mononeuropathy. Complaints of a 77-year-old man started with pain in his right arm and 4 days later he developed itchy red HZ lesions in the same area. One week later, the patient developed weakness in his right arm. The patient was diagnosed with isolated axillary mononeuropathy by physical examination and electromyography. Here, we present a case of axillary mononeuropathy which is a rare complication of HZ infection and needs particular attention.

Clinical Neuroscience

[Multiple ischemic stroke in Osler-Rendu-Weber disease]

SALAMON András, FARAGÓ Péter, NÉMETH Viola Luca, SZÉPFALUSI Noémi, HORVÁTH Emese, VASS Andrea, BERECZKY Zsuzsanna, TAJTI János, VÉCSEI László, KLIVÉNYI Péter, ZÁDORI Dénes

[Hereditary hemorrhagic teleangiectasia (HHT, Osler-Rendu-Weber disease) is an autosomal dominantly inherited disorder caused by the mutation of several possible genes and characterized by malformations of the arteriovenous system in multiple organs. The clinical diagnosis is based on the Curaçao criteria ((1) spontaneous, recurrent epistaxis; (2) teleangiectasias in characteristic sites (lips, oral cavity, nose, fingers); (3) visceral lesions (gastrointestinal, pulmonary, cerebral, spinal); (4) affected first degree relative). The aim of this study is to present the first genetically confirmed Hungarian case of hereditary hemorrhagic teleangiectasia with multiple ischemic strokes. Our 70-year-old woman has been suffering from severe epistaxis since her childhood and presented gastrointestinal bleeding during her adulthood as well. The characteristic skin lesions developed in the 5th decade of life. She was admitted to our department with loss of consciousness and fluctuating speech and swallowing problems. MRI of the brain supplemented with angiography revealed multiple arteriovenous malformations and multiple subacute ischemic lesions. The EEG demonstrated slowing of electric activity in the left frontal lobe. The neuropsychological assessment showed deficits in anterograde memory and executive functions. The diagnostic work-up for other characteristic alterations identified an arteriovenous malformation in the left lung. The genetic analysis demonstrated a heterozygous mutation in the 7th exon of the ENG gene at position 834 resulting in a thymine duplication and an early stop codon by a frame shift. The present case is largely similar to those already described in literature and draws the attention to the importance of multidisciplinary collaboration in the care of HHT patients.]

Clinical Neuroscience

[Selection of the optimal device-aided therapy in Parkinson’s disease]

KOVÁCS Norbert, ASCHERMANN Zsuzsanna, JUHÁSZ Annamária, HARMAT Márk, PINTÉR Dávid, JANSZKY József

[For the treatment of advanced Parkinson’s disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary. Although they may have similar impact on the health-related quality of life and disabilities associated with the disease, they have different indications, and inclusion- and exclusion criteria. Consequently, the patient population treated with DBS and LCIG may be different. In the present review, the authors try to help the process of selection of the optimal device-aided therapy for the patients with advanced Parkinson’s disease. ]

All articles in the issue

Related contents

Clinical Neuroscience

[Current questions of multiple sclerosis: the secunder progressive form of the disease]

VÉCSEI László

[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]

Clinical Oncology

[Biomarkers - today and tomorrow]

KOPPER László

[Biomarkers (tumor markers in oncology) are able to make exact, objective and reproducible distinction between two groups. Biomarkers can serve different purposes, as to estimate the patient’s survival without treatment (prognostic marker), to select those patients who would respond optimally to treatment (predictive marker), to follow the patient in order to detect of a relapse (monitoring marker), helping identifi cation the tumor-type (diagnostic marker). The main task for a biomarker is to find the best treatment with less toxicity. The main enemy of biomarkers is the heterogeneity of the tumor, the continuous change in its geno- and phenotype, which can explain the low sensitivity and specifi city. More attention should be given to standardization and validity. It is highly possible, that biomarker-panel as well as marker-based clinical trials will be used in the near future.]

Clinical Oncology

[Gene-expression profiles in adjuvant treatment of early breast cancer]

PAJKOS Gábor

[Breast cancer is a heterogeneous disease with different subtypes having a distinct biological, molecular, and clinical course. Assessments of standard clinical and pathological features have traditionally been used to determine the use of adjuvant systemic therapy in early-stage breast cancer; however, the ability to identify those who will benefi t from adjuvant chemotherapy remains a challenge, leading to over treatment of some patients. Risk stratifi cation of patients with early stage breast cancer may support adjuvant chemotherapy decision-making. This review details the development and validation of seven multi-gene classifi ers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test’s analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use.]

Clinical Neuroscience

[GENETIC BACKGROUND OF HUMAN PRION DISEASES]

KOVÁCS Gábor Géza

[acquired. The human prion protein gene (PRNP) is located to chromosome 20 (20p12-ter). Mutations and polymorphisms in the PRNP are associated with prion disease. Genetic prion diseases are inherited in an autosomal dominant trait, examination of the penetrance is restricted to mutation E200K (59-89%). Mutations can be substitutions or insertions. Genetic prion diseases are classified according to the clinicopathological phenotype and comprise genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia. Base pair insertions may resemble Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker disease phenotypes, however, their unique clinicopathological presentations are also emphasized. Among the polymorphisms of the PRNP, the one at codon 129 is the most important, where methionine or valine may be encoded. This polymorphism is known to influence the phenotype of disease forms. Molecular classification of sporadic Creutzfeldt-Jakob disease also depends on the codon 129 polymorphisms in addition to the Western blot pattern of the protease resistant prion protein. According to this at least six well characterised forms of sporadic Creutzfeldt-Jakob disease are known. Influence of other genes were also investigated. Contrasting results are reported regarding the role of apolipoprotein E allele ε4, but presence of allele ε2 seems to influence the prognosis. Polymorphisms in the doppel gene or ADAM10 could not be clearly associated with Creutzfeldt-Jakob disease. Polymorphisms in the upstream and intronic regulatory region of the PRNP gene may be a risk factor for Creutzfeldt-Jakob disease. The PRNP codon 129 polymorphism was examined in non-prion diseases. Some studies suggest that this polymorphism may have influence on the cognitive decline and early onset Alzheimer’s disease.]

Clinical Oncology

[Mucositis - prevention and therapy]

NAGY Zsuzsanna, VALTINYI Dorottya

[Side-effects are critical challenges in cancer therapy. These complications can threaten the quality of life, sometimes the life itself. One of the most frequent side effects is mucositis, the damage of mucosa, either in the oral cavity (oral mucositis, OM), or in the gastrointestinal tract (gastrointestinal mucositis, GIM). Prevention is a key action for the effi cient supportation. Recognition of OM is relative easy, but of GIM is rather diffi cult. The risk factors could come from the patients and/or can be caused by the therapy. The successful management of mucositis mostly depends on the cooperation of the patient, which is highly infl uenced by the success of care (e.g. decreasing the level of pain). In general, mucositis (especially oral mucositis) a well managable disease, burt more informations are required to increase the quality of prevention and therapy. Such expectation could be realized by specifi c and sensitive biomarkers, however, they are still missing]