Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer's Disease.

This study investigated the diagnostic accuracy of plasma biomarkers-specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer's disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group of cognitively unimpaired (CU) individuals. Neuroradiological assessments included brain magnetic resonance imaging (MRI) following dementia protocols, with subsequent volumetric analysis. Additionally, cerebrospinal fluid (CSF) AD biomarkers were classified using the A/T/N system, and apolipoprotein E (APOE) ε4 carrier status was determined. Findings revealed elevated plasma levels of MMP-9 and TIMP-1 in AD dementia patients compared to CU individuals. Receiver operating characteristic (ROC) curve analysis demonstrated significant differences in the areas under the curve (AUC) for MMP-9 (p < 0.001) and TIMP-1 (p < 0.001). Notably, plasma TIMP-1 levels were significantly lower in APOE ε4+ patients than in APOE ε4- patients (p = 0.041). Furthermore, APOE ε4+ patients exhibited reduced hippocampal volume, particularly in total, right, and left hippocampal measurements. TIMP-1 levels exhibited a positive correlation, while the MMP-9/TIMP-1 ratio showed a negative correlation with hippocampal volume parameters. This study sheds light on the potential use of TIMP-1 as a diagnostic marker and its association with hippocampal changes in AD.

Peripheral glutamate and TNF-α levels in patients with intracerebral hemorrhage: Their prognostic values and interactions toward the formation of the edemal volume.

OBJECTIVE: We aimed to evaluate the prognostic values, contribution and interactions of the peripheral blood plasma glutamate and tumor-necrosis factor-α (TNF-α) levels toward the formation of the perifocal edema in patients with intracerebral hemorrhage (ICH). METHODS: Fifty patients with ICH and fifty healthy controls were included in the study. The peripheral markers were detected by high-sensitivity ELISA. RESULTS: A highly significant differences in plasma glutamate and TNF-α levels with good separation of their values was detected between patients and healthy controls. The two variables correlated with the severity of the symptoms and the initial volume of the ICH at admission. Both peripheral glutamate and TNF-α levels at admission were estimated as significant predictors for the formation of the perifocal edema five days after ICH; nevertheless, it was shown that they independently contribute to the development of the edema, without effects of interaction and regardless the localization of the ICH. CONCLUSIONS: Our results support the idea for the significance of glutamate and TNF-α as peripheral markers for excitotoxicity and inflammation in ICH patients. The developed multiple regression model for prediction of the development of the edema could be beneficial in decision making between conservative treatment and surgical intervention in the clinical practice.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common and best known monogenic small vessel disease. Here, we review the clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on the most relevant articles published between 1994 and 2016 and on the personal experience of the authors, all directly involved in CADASIL research and care. We conclude with some suggestions that may help in the clinical practice and management of these patients.

Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol.

OBJECTIVE: To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. RESULTS: Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). CONCLUSION: In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. KEY POINTS: Gadolinium deposition may occur within the human brain after multiple gadolinium contrast administrations. Increasing T1W signal intensity occurs within the dentate nucleus and globus pallidus. Increasing signal intensity may be a consequence of multiple administrations of gadobutrol. Administration of gadobutrol over a shorter period causes greater signal intensity increase.

Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status.

INTRODUCTION: Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. METHODS: Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. RESULTS: Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. CONCLUSION: Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs.

The role of magnetic resonance imaging in the evaluation of endometrial carcinoma.

PURPOSE: Gynecological cancers comprise about 19% of all cancers in women whereas the endometrial cancer is the most common malignant tumor of the female reproductive organs. The application of modern imaging tools plays an important role in the preoperative assessment of disease extent and allows the selection of a proper and adequate therapeutic approach for each patient. The purpose of this review was to show the role of magnetic resonance imaging (MRI) in the evaluation of endometrial carcinoma. MRI enables the display of zonal anatomy of the uterus, detection of the anomalies as well as the detection and characterization of pathological processess. Endometrial cancer is staged with the International Federation of Gynecology and Obstetrics (FIGO) classification, which was significantly revised in 2009. The FIGO classification incorporates two of the important prognostic parameters, the depth of myometrial invasion and histological grade. The depth of myometrial invasion can be accurately assessed by MRI. MRI is not officially included in the FIGO staging system. However, it is widely accepted as a suitable imaging technique for preoperative staging, treatment planning and monitoring of patients with endometrial cancer.

Alternaria-Associated Fungus Ball of Orbit Nose and Paranasal Sinuses: Case Report of a Rare Clinical Entity.

Alternaria-associated fungus ball of maxillar, ethmoidal paranasal sinuses, nasal cavity and orbit with bone erosion is extremely rare. Till recently, only two cases of this infection in immune competitive patients have been reported. We are herein describing the case of immune-competent woman who suffered of nasal congestion for 10 years. Patient was treated for tumor-like lesion in right maxillar sinus, where propagation in right nose cavity, right ethmoidal cells and right orbita was present. The organism that was seen in surgical removal of fungal debris by histological study, in using mycological testing, was proven as Alternaria alternata. Combination of surgical intervention and treatment with itraconazole eradicated fungal infection, and the disease was not relapsed in follow-up period of 2 years.

Primary and salvage total laryngectomy. Influential factors, complications, and survival.

PURPOSE: In this retrospective study we analysed patients with advanced squamous cell carcinoma of the larynx and hypopharynx treated with primary total laryngectomy (PTL) between 1990 and 2007. METHODS: The patients were treated by classical PTL, radiotherapy 60-70 Gy, concomitant radio and chemotherapy (cisplatin and 5-fluorouracil) or salvage total laryngectomy (STL). They were followed up for 5 years and complications, survival, residual/recurrent disease and metastases were registered. RESULTS: STL after previous radiotherapy (STL-pRT), and after chemoradiotherapy (STL-pCTRT) caused more frequent local complications than PTL. Five-year disease-free survival (DFS) rate was significantly influenced by TNM stage and localization of the primary laryngeal tumor. For laryngeal cancer it was: 61.3% for PTL, 54.1% for STL-pC-TRT, and 47.6% for STL-pRT. Incomplete responders to initial treatment had low survival rate. PTL for hypopharyngeal carcinoma and particularly salvage laryngectomy after chemoradiotherapy were associated with more frequent local complications. The 5-year DFS for hypopharyngeal cancer was lower than for laryngeal cancer. CONCLUSION: PTL still offers the best survival rate with low complications for advanced laryngeal and hypopharyngeal squamous cell carcinoma. STL causes more frequent local complications, especially after chemoradiotherapy. Addition of chemotherapy to radiotherapy increases the survival. Five-year DFS rate depends on TNM stage and localization of the primary tumor.

Glutathione homeostasis disruption of erythrocytes, but not glutathione peroxidase activity change, is closely accompanied with neurological and radiological scoring of acute CNS inflammation.

OBJECTIVES AND METHODS: The levels of glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in the erythrocytes of 50 patients with clinically isolated syndrome of CNS (CIS) and 57 patients with relapsing remitting multiple sclerosis (RRMS). RESULTS: A decrease in GSH content and GPx activity showed significance in both study groups compared to the control values (p = 0.0025 and 0.007 for GSH and p = 0.005 and 0.003 for GPx, in CIS and RRMS patients, respectively). The depletions were more pronounced in RRMS than in CIS patients (p = 0.009 for GSH and p = 0.031 for GPx). The results significantly verify the negative correlations between GSH values and clinical severity (r = -0.513, p = 0.004), radiological findings (r = -0.351, p = 0.008) and disease duration (r = -0.412, p = 0.0025) in CIS patients. The same correlations were observed in RRMS patients between GSH values and clinical severity (r = -0.498, p = 0.004) and patients' radiological features (r = -0.454, p = 0.005). No correlations were observed between GSH values and other patient characteristics, or between GPx activity and all tested patient characteristics (p > 0.01). CONCLUSIONS: The results indicate that GSH content and GPx activity both decreased below the normal range and were accompanied with neuroinflammation, but although both might have great importance in neuroinflammation development, the data presented here confirm that only GSH might serve as a marker which is closely correlated with neurological and radiological scoring of acute CNS inflammation.

Cerebrospinal fluid and plasma oxidative stress biomarkers in different clinical phenotypes of neuroinflammatory acute attacks. Conceptual accession: from fundamental to clinic.

Oxidative stress is revealed as the main contributor in the pathophysiology of neuroinflammation. Analyzing plasma and cerebrospinal fluid (CSF) of patients with different clinical phenotypes of neuroinflammation, defined as clinically isolated syndrome (CIS), and those defined as relapsing remitting multiples sclerosis (RRMS), we tested peripheral and CNS oxidative stress intensity in these neuroinflammatory acute attacks. All obtained values changes were assessed regarding clinical and radiological features of CNS inflammation. The obtained results revealed an increase in malondialdehyde levels in plasma and CSF in CIS and RRMS patients compared to control values (p < 0.05). The obtained values were most prevailed in both study group, CIS and RRMS, in patients with severe clinical presentation (p < 0.05). Measured activities of catalase and total superoxide dismutase were higher in CIS and RRMS patients in plasma compared to control values (p < 0.05), parallel with an increased catalase activity and decrease in superoxide dismutase activity in CSF regarding values obtained in control group (p < 0.05). The positive correlations regarding clinical score were obtained for all tested biomarkers (p < 0.01). Although the positive correlations were observed in MDA levels in plasma and CSF, for both study patients, and their radiological findings (p < 0.01), and a negative correlation in plasma SOD activity and CIS patients' radiological findings (p < 0.01), no other similar correlations were obtained. These findings might be useful in providing the earliest antioxidative treatment in neuroinflammation aimed to preserve total and CNS antioxidative capacity parallel with delaying irreversible, later neurological disabilities.

Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks.

In order to examine the endogenous antioxidants values in the earliest phase of demyelination, we have determined bilirubin and uric acid (UA) serum values in the patients with clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS), regarding their clinical disability, measured by Extended Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), disease duration, gender and other parameters. The bilirubin and UA levels were lower in CIS and RRMS patients than in control group, whether male or female (p < 0.05). The bilirubin and UA levels were decreased in RRMS compared to CIS patients (p < 0.05). Regarding EDSS, MRI and disease duration, obtained values of bilirubin and UA were higher in both study groups in patients with lower EDSS, lower MRI lesion number and shorter disease duration (p < 0.05). The greatest significance in decreased bilirubin and UA levels was observed in female compared to male patients, in both study groups (p < 0.05). The results suggest negative linear correlation between bilirubin and UA levels and disease duration, EDSS and MRI in CIS (p < 0.01), with the same correlation between bilirubin and UA levels and disease duration in RRMS patients (p < 0.01). There was also significant correlation between bilirubin level and MRI findings and UA levels and EDSS in RRMS patients (p < 0.01). The obtained results point to the importance of endogenous antioxidants in the outbreak and course of neuroinflammation. This could be favorable for the new pathogenetically conditioned neuroinflammatory therapy concepts which do not initially rely only on immunomodulatory, but also on the antioxidative effects.

The role of magnetic resonance imaging in the diagnosis and prognosis of dementia.

Dementia is a syndrome characterized by multidomain acquired chronic cognitive impairment that has a profound impact on daily life. Neurogenerative diseases such as Alzheimer's disease or nondegenerative diseases such as vascular dementia are considered to cause dementia. The need for further diagnostic improvement originates from the prevalence of these conditions, especially in developed countries with a predominance of the elderly population. Today, the diagnosis and follow-up of all neurodegenerative diseases cannot be performed without radiological imaging, primarily magnetic resonance imaging (MRI). The introduction of 3T MRI and its modern techniques, such as arterial spin labeling, has enabled better visualization of morphologic changes in dementia. For better diagnosis and follow-up in patients with dementia, various semiquantitative scales have been designed to improve the accuracy of assessment and decrease interobserver variability. Moreover, there is a growing need for MRI in the assessment of novel therapies and their side effects. To better apply MRI findings in the diagnosis of both already developed dementia and its early stages, the aim of this paper is to review the available literature and summarize the specific MRI changes.

Influential factors, complications and survival rate of primary and salvage total laryngectomy for advanced laryngeal cancer.

This is a retrospective review of patients with advanced malignant neoplasms of the larynx treated with total laryngectomy. 387 total laryngectomies for advanced squamous cell carcinoma of larynx performed in the period between 1995 and 2007 were analyzed. Primary total laryngectomy (PRT) was performed in 316 patients, while initial radiotherapy radiotherapy (60-70 Gy) and concomitant chemotherapy (cisplatin-5 fluorouracil) with radiotherapy were applied in totally 71 patients who later received salvage total laryngectomy (STL). All the laryngectomies were performed by four surgeons, using the same routine surgical technique. Postoperative clinical examination was made every three months during five years. We documented the occurrence of: local and general complications, survival rate, residual and recurrent disease, lymph node metastasis, and other changes. Salvage total laryngectomy after previous radiotherapy (STL-pRT) and after chemoradiotherapy (STL-pCTRT) caused more frequent local complications than primary total laryngectomy (PTL). TNM stage and localization of primary laryngeal tumor had significant influence on five year survival rate. It amounted: 61.4% for PTL, 52.6% for STL-pCTRT, and 48.5% for STL-pRT. Incomplete response to initial treatment produced low survival rate. Salvage total laryngectomy caused more frequent local complications, especially after chemoradiotherapy when compared to primary laryngectomy. Survival rate was increased when chemotherapy is added to radiotherapy. Five year survival rate depended on TNM stage and localization of primary tumor.

Prediction of in-hospital mortality after acute upper gastrointestinal bleeding: cross-validation of several risk scoring systems.

OBJECTIVE: We aimed to identify the clinical, biochemical, and endoscopic features associated with in-hospital mortality after acute upper gastrointestinal bleeding (AUGIB), focusing on cross-validation of the Glasgow-Blatchford score (GBS), full Rockall score (RS), and Cedars-Sinai Medical Center Predictive Index (CSMCPI) scoring systems. METHODS: Our prospective cross-sectional study included 156 patients with AUGIB. Several statistical approaches were used to assess the predictive accuracy of the scoring systems. RESULTS: All three scoring systems were able to accurately predict in-hospital mortality (area under the receiver operating characteristic curve [AUC] > 0.9); however, the multiple logistic model separated the presence of hemodynamic instability (state of shock) and the CSMCPI as the only significant predictive risk factors. In compliance with the overall results, the CSMCPI was consistently found to be superior to the other two systems (highest AUC, highest sensitivity and specificity, highest positive and negative predictive values, highest positive likelihood ratio, lowest negative likelihood ratio, and 1-unit increase in CSMCPI associated with 6.3 times higher odds of mortality), outperforming the GBS and full RS. CONCLUSIONS: We suggest consideration of the CSMCPI as a readily available and reliable tool for accurately predicting in-hospital mortality after AUGIB, thus providing an essential backbone in clinical decision-making.

A case of complex arteriovenous malformation with skull destruction presented in sixth decade of life.

Intracranial AVMs are typically diagnosed before the patient has reached the age of 40 years, and a few cases have been reported of AVM with skull destruction. We described a rare case of a complex cerebral AVM with skull destruction, presented de novo in 52-year-old woman with epileptic seizures. Neuroimaging investigations revealed complex AVM in right hemisphere as well as extracranially, with signs of skull destructions, likely caused by significant involvement of feeders from external carotid artery. Neurosurgery treatment was not recommended due to morphological characteristics and drainage patterns of the AVM. EEG investigation showed discrete specific activity in correspondent area and pharmacology treatment for seizures was initiated. One year after the initial presentation patient had survived rebleeding episode witch left permanent neurology deficit. This patient considered as a rare case of complex AVM with skull destruction, presented de novo in sixth decade of life.

ASL perfusion in acute ischemic stroke: The value of CBF in outcome prediction.

OBJECTIVE: The application of novel advanced magnetic resonance imaging (MRI) techniques in clinical practice has significantly improved diagnostic accuracy in early detection of acute ischemic stroke (AIS), additionally allowing outcome prediction. The introduction of arterial spin labeling (ASL) perfusion sequence as a standard in MRI protocols is a significant milestone in neuroradiology. The aim of the present study was to demonstrate the potential of ASL sequence for the detection of absolute (aCBF) and relative (rCBF) cerebral blood flow values for an ischemic area and to examine the correlation of the obtained values with the functional outcome of patients. PATIENTS AND METHODS: The study included 205 patients of both sexes over the age of 18 years, suspected with AIS, who met the inclusion criteria. Brain MRI examination according to the protocol for ischemia with fast three-dimensional pseudocontinuous (3D PCASL) ASL technique was used. Statistical analysis of the collected data was performed with SPSS 15.0. RESULTS: The appearance of the ROC curve indicated good diagnostic characteristics of aCBF in assessing a favorable stroke outcome, demonstrating a high statistical significance (p < 0.001), and high conclusion validity. The value of the rCBF was significantly higher in patients with a favorable outcome compared with patients with a poor outcome (p  < 0.001). The sum of sensitivity and specificity was the highest using aCBF cut-off value of 19.140 mL/100 g/min, and rCBF cut-off of 49.700 of the contralateral side percentage value. CONCLUSION: Our study shows that ASL perfusion sequence allows precise detection of perfusion values and provides a reliable insight into outcome prediction.

Endovascular treatment of hereditary hemorrhagic telangiectases of the tongue.

Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is an autosomal dominant disorder involving vascular abnormalities of various organs. Telangiectases are frequently observed, predominantly on the nasal and oral mucosa. We present a case a of 53-year-old man with the tonge hemorrhagic telangiectases and epistaxis. Selective catheterization and embolization of the right lingual artery led to size redution and no bleeding from tongue telangiectases.

[Reversible Paraplegia - Favorable Outcome After Delayed Diagnosis]. / Reversible Paraplegie ­ erfreulicher Ausgang bei verzögert gestellter Diagnose.

Reversible Paraplegia - Favorable Outcome After Delayed Diagnosis Abstract. A 74-year-old woman was referred for progressive gait disturbances. On presentation, she had a complete paraplegia (wheelchair-bound for 19 months) and bladder sphincter dyssynergia with sensory sacral sparing. Magnetic resonance imaging studies revealed a 24 × 13 × 17 mm intradural mass with compression of the spinal cord and myelomalacia between C6 and Th1. We performed unilateral laminectomies of C6-Th1 and microsurgical resection of a meningioma. Under intensive rehabilitation, the patient regained independent walking ability and recovery of bladder function and continence within six months postoperatively.