Association of Mediterranean diet adherence with disease progression, quality of life and physical activity, sociodemographic and anthropometric parameters, and serum biomarkers in community-dwelling older adults with multiple sclerosis: a cross-sectional study.

BACKGROUND: Multiple sclerosis (MS) constitutes a chronic inflammatory and degenerative demyelinating disease, which can progressively lead to a broad range of sensorimotor, cognitive, visual, and autonomic function symptoms, independently of patient' age. However, the clinical studies that examine the role of dietary patterns against disease progression and symptomatology remain extremely scarce, especially concerning Mediterranean diet (MD) in the subgroup age of older adults with MS. AIMS: The present study aimed to investigate the potential impact of MD compliance in disease progression and symptoms severity as well as quality of life and physical activity of community-dwelling older adults with MS. METHODS: This is a cross-sectional conducted on 227 older adults with no history of other severe disease. Relevant questionnaires were applied to collect sociodemographic and anthropometric factors by face-to face interviews between patients and qualified personnel. Serum biomarkers were retrieved by patients' medical records. RESULTS: Higher MD compliance was independently associated with younger patients' age, lower risk of overweight/obesity and abdominal obesity, decreased disease progression and higher muscle mass, as well as greater physical activity, better quality of life, and adequate serum ferritin and albumin levels CONCLUSIONS: MD may exert beneficial effects in older adults with MS. Future strategies and policies are highly recommended to inform both the general population and the older patients with MS for the beneficial effects of MD in preventing MS and in improving or even slowing down the disease progression and symptoms severity of MS.

Associations between Mediterranean Diet Adherence, Quality of Life, and Mental Health in Patients with Multiple Sclerosis: A Cross-Sectional Study.

BACKGROUND: The Mediterranean diet (MD) is well-known as a diet which may exert a protective effect against neurodegenerative diseases, including multiple sclerosis (MS). To date, only a few clinical surveys have assessed the potential effects of the MD in patients with MS. The purpose of the present study is to evaluate the potential effects of MD compliance on disease disability, quality of life, physical activity, depressive symptomatology, and blood biochemical parameters related to nutritional status in MS patients, considering several socio-demographic, anthropometric, and lifestyle characteristics. METHODS: This is a cross-sectional study conducted on 558 adults with MS aged 18-64 years. Relevant questionnaires were utilized to evaluate socio-demographic and anthropometric parameters, disease disability (Expanded Disability Status Scale, EDSS), multidimensional health-related quality (MS Quality of Life-54, MSQOL-54), physical activity levels (International Physical Activity Questionnaire, IPAQ), depression (Beck Depression Inventory II, BDI-II), and MD adherence (MedDietScore), while several blood biochemical parameters were retrieved from the patients' medical records. RESULTS: Enhanced MD compliance was independently associated with a decreased frequency of overweight/obesity, as well as abdominal obesity, in patients suffering from MS. Elevated MD compliance was also independently associated with a decreased incidence of advanced disease disability, a higher prevalence of elevated physical activity, an improved quality of life, and lower depressive symptoms, as well as higher levels of certain blood biochemical parameters, which are effective indicators of iron deficiency and malnutrition. CONCLUSIONS: The present study found that higher MD adherence may slow down disease disability, promoting a better quality of life and mental health in adults with MS. Future prospective surveys are required to obtain conclusive results.

Comprehensive tumor molecular profile analysis in clinical practice.

BACKGROUND: Tumor molecular profile analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Programmed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly. METHODS: In the present study, tumor molecular profile analysis was performed using a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied. RESULTS: Molecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or off-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers' analysis in 191 cases increased the number of patients with an on-label treatment recommendation by 22.92%, while an option for on-label or off-label treatment was provided in 71.35% of the cases. CONCLUSIONS: Tumor molecular profile analysis using NGS is a first-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eligible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of treatment strategy.

West Nile neuroinvasive disease. Report of four cases in Northern Greece, 2018.

West Nile virus (WNV) is a mosquito-borne RNA flavivirus which caused several epidemics worldwide. The year 2018 was a WNV record year for Europe, including Greece, with earlier and longer transmission season with higher than the previous number of cases. It has been proposed that some simple biochemical markers may be helpful for the recognition of WNV neuroinvasive disease, its differential from other neurological infectious diseases and prognosis. We describe four cases that suffered from WNV meningitis and/or encephalitis hospitalized in 2018 in a tertiary hospital in Thessaloniki, Greece, and investigate the importance of simple biomarkers for the recognition of WNV etiology.

Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer's disease.

Background Alzheimer's disease (AD) is the most prevalent form of dementia. Currently, the most studied biomarkers of AD are cerebrospinal fluid (CSF) amyloid ß 1-42, total tau and phosphorylated tau. However, misdiagnosis can exceed 20%. Recently, we found that CSF amyloid ß precursor-like protein-1 (APLP1) and neuronal pentraxin receptor (NPTXR) are promising biomarkers of AD. The aim of the present study is to validate CSF APLP1 and NPTXR as biomarkers of AD severity. Methods APLP1 and NPTXR concentrations were measured in the CSF of patients with mild cognitive impairment (MCI) (n = 14), mild AD (n = 21), moderate AD (n = 43) and severe AD (n = 30) using enzyme-linked immunosorbent assays (ELISAs). Results CSF APLP1 and NPTXR were not associated with age or sex. CSF APLP1 was not different between any of the AD severity groups (p = 0.31). CSF NPTXR was significantly different between MCI and mild AD (p = 0.006), mild and moderate AD (p = 0.016), but not between moderate and severe AD (p = 0.36). NPTXR concentration progressively declined from MCI to mild, to moderate and to severe AD patients (p < 0.0001, Kruskal-Wallis test). CSF NPTXR positively correlated with the Mini-Mental Status Examination (MMSE) score (p < 0.001). Conclusions NPTXR concentration in CSF is a promising biomarker of AD severity and could inform treatment success and disease progression in clinical settings.

Evaluation of the cholinergic hypothesis in Alzheimer's disease with neuropsychological methods.

AIM: This study aimed at evaluating the cholinergic hypothesis in Alzheimer's disease (AD) patients utilizing the pupillometry method, cognitive tests and Hamilton Depression Rating Scale (HAM-D), as well as to examine whether a correlation between cognitive tests and pupillometry exists. METHODS: Forty-two patients with mean age 69.2 ± 7.0 years and documented AD volunteered to participate in this study, while 33 healthy matched subjects served as controls. All subjects underwent a pupillometric measurement and performed the Wechsler Memory Scale (WMS) and Mini Mental State Examination (MMSE). Also, HAM-D was used to assess the severity of depressive symptoms. The pupillometric parameters studied were (1) latency for the onset of constriction (T1), (2) maximum constriction velocity (VCmax), and (3) maximum constriction acceleration (ACmax). RESULTS: In AD patients MMSE and WMS score were correlated with ACmax (r = -0.409, p < 0.05 and r = -0.513, p < 0.05, respectively) and VCmax (r = -0.664, p < 0.05 and r = -0.771, p < 0.05), respectively. Moreover, T1 was found to be significantly increased by 23 % (p < 0.05) in AD patients compared to healthy subjects. Conversely, the mean scores of VCmax and ACmax were significantly decreased in AD patients by 46 % (p < 0.05) and by 47 % (p < 0.05), respectively, as compared to healthy subjects. There was no significant difference between the two groups for HAM-D. Additionally, AD patients showed decreased score in WMS by 40 % (p < 0.05) and in MMSE by 28.5 % (p < 0.05) compared to healthy subjects. Of the indices that were studied VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System. CONCLUSIONS: The results of this study demonstrated that there is a correlation between cognitive tests and pupillometry in AD patients. Thus, pupillometry could be considered as a sensitive technique for the investigation of cholinergic deficits, which indirectly lead to memory and cognitive disorders in AD patients.

Hippocampal neuronal loss in the CA1 and CA3 areas of Alzheimer's disease patients.

BACKGROUND: It is believed that in Alzheimer's disease (AD) some areas of the brain are particularly vulnerable to specific degenerative processes and that they could exhibit neuronal dysfunction in the earliest stage of the disease. The implications of the hippocampus in memory processes are very well known and it is likely that the hippocampus would be among the first areas of the brain affected by the pathogenic mechanisms occurring in AD. However, the distinction between the neurodegenerative changes that accompany normal ageing and those that characterize AD is not clear. Also, the distribution of the hippocampal cell loss in both normal aging and AD is not very well understood. SUBJECTS AND METHODS: In this context, we focused on the quantification of the neuronal density in the four specific areas of the hippocampus (CA1-CA4) of AD brains, as compared to an age-matched control group, by using the Nissl staining technique. RESULTS: We found a significant reduction of neuronal density especially in the CA1 and CA3 hippocampal areas. The most prominent decrease was found at the CA1 area level, as compared to all other 3 areas which were analyzed. CONCLUSIONS: In the present study we managed to demonstrate and confirm a significant neuronal loss of hippocampus in AD, as compared to an age-matched control group. Moreover, it seems that this decrease of hippocampal neuronal density is more prominent especially at the CA1 and also in the CA3 hippocampal areas. This could have important implications in the design of therapeutic and investigative strategies of AD. However, larger samples are necessary in order to provide the basis for firmer conclusions in this area of research.

Pupillometry and 123I-DaTSCAN imaging in Parkinson's disease: a comparison study.

The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinson's disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)-nortropane]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and (123)I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems.

Dendritic pathology and spinal loss in the visual cortex in Alzheimer's disease: a Golgi study in pathology.

Alzheimer's disease is a neurodegenerative disorder characterized by progressive decline in memory, loss of professional skills, impairment of judgement and behavior, and decline in social performances. In terms of neuropathology, the morphological hallmarks of the disease are the accumulation of alpha-beta peptide and the neurofibrillary degeneration, associated with synaptic alterations, involving mostly the dendritic spines. This study is based on the morphological analysis of 10 brains, 5 of which were obtained from patients who suffered from Alzheimer's disease and 5 from nondemented senile individuals used as control group. The segments taken in major from the occipital lobe were studied with the use of Golgi method, as well as Gallyas' and Bielschowski' s staining methods. In most of the pyramidal cells in the affected brains, there seems to be important spine loss and extensive dendrite pathology. Apical dendrites are distorted and tortuous. Horizontal dendritic arborization is severely decreased leading to an amputated, bell-shaped cell soma. Senile plaques have been often revealed, and neurofibrillary changes have also been noticed.

The use of pupillometry in the assessment of cardiac autonomic function in elite different type trained athletes.

The aim of the present study was to evaluate cardiac autonomic function by pupillometry in male athletes. Fifteen elite endurance- (END) and eleven power-trained (POWER) athletes and fifteen sedentary individuals (CONTROL) were studied. All subjects underwent three pupillometric measurements: at rest, peak exercise testing and recovery phase. The pupillometric indices studied were: baseline pupil radius (R1), minimum pupil radius (R2), maximum constriction velocity (VC(max)), maximum constriction acceleration (AC(max)), amplitude (AMP, R1-R2), constriction ratio (AMP%). During exercise, RR intervals were obtained for each subject with a Polar S810i for time and frequency domain heart rate variability (HRV) analysis. The following parameters of HRV were measured: standard deviation of all NN intervals (SDNN), the mean square successive differences (rMSSD), percent of NN intervals differing >50 ms from the preceding NN (pNN50), low (LF)- and high (HF)- frequency components of the autoregressive power spectrum of the NN intervals and their ratio (LF/HF). At rest and recovery, END showed significantly increased VC(max) and AC(max) compared to POWER and CONTROL. AMP% was significantly greater in END at rest, peak exercise and recovery compared to POWER and CONTROL. END and POWER had significantly greater AMP at rest and recovery compared to CONTROL. Moreover, all HRV indices were significantly increased in END compared to POWER and CONTROL. However, POWER showed significantly increased rMSSD and LF compared to CONTROL. HRV parameters were significantly correlated with pupillometric parameters during exercise. Our results indicated that any kind of exercise training and mainly endurance one affects autonomic regulation of pupillary light reflex.

Pupil light reflex in Parkinson's disease: evaluation with pupillometry.

We evaluated pupil light reflex (PLR) in patients with Parkinson's disease (PD) and normal controls by means of pupillometry and explored its possible relation to clinical characteristics in parkinsonian patients. PLR was evaluated using pupillometry in 66 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited by single flash stimuli of 24.6 candelas/m(2) intensity and 20 ms duration, and six parameters were studied after full recording of pupil's movement. A significant increase in latency (T1) and significant decrease in amplitude (R1-R2), maximum constriction velocity (V(max)), as well as maximum acceleration (AC(max)) was found in parkinsonian patients. There was no significant difference in initial radius (R1) and minimum radius (R2) values. Of the parameters studied, AC(max) emerged as a significant predictor for discrimination between PD patients and controls. There was no significant correlation between pupillometry parameters and clinical characteristic of patients (disease duration, stage, and the Unified Parkinson's Disease Rating motor scale). The study demonstrates PLR disorder in PD patients even without overt clinical autonomic dysfunction. Pupillometry appears to be a useful and noninvasive method for exploration of PLR alterations in PD and may prove to be useful for the early detection of subclinical autonomic nervous system dysfunction.

Morphological changes of the human purkinje cells and deposition of neuritic plaques and neurofibrillary tangles on the cerebellar cortex of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder, characterized by progressive decline in memory and in social performance. The morphological hallmarks of the disease are neuronal loss, loss of dendritic spines, neurofibrillary degeneration and neuritic plaques mainly in the hippocampus and the cortex of the cerebral hemispheres. This study is based on the morphological analysis of the cerebellar cortices of eight brains, 4 patients suffered from Alzheimer's disease and 4 normal controls, by Golgi method, as well as Nissl, Gallyas', Bielschowsky's, Methenamine Silver staining and Congo red methods. Although typical neuritic plaques were not seen in the cerebellar cortex and the diffuse plaques found in the cerebellum in far smaller proportion than plaques in the prefrontal and parietal cortices of the same cases, Golgi impregnation technique revealed a loss of Purkinje cells and a marked decrease in the density of dendritic arborization.

Pupillometric characteristics in patients with choroidal neovascularization due to age-related macular degeneration.

PURPOSE: To study the pupillary light reflex in patients with choroidal neovascularization due to age-related macular degeneration (AMD). METHODS: The study included 15 patients with AMD and 15 control subjects. A full recording of the pupil's reaction to light was registered and the following eight parameters were measured and reported: baseline pupil (R1), latency (T1), minimum pupil radius (R2), amplitude (AMP), maximum constriction velocity (VCmax), maximum constriction acceleration (ACmax), time for maximum velocity (T2), and time for maximum constriction (T3). RESULTS: All variables measured presented alterations in the AMD group and a number of them were significantly reduced in the AMD group. CONCLUSIONS: The presence of neovascular AMD significantly affects the pupil's response to light stimulus when compared to normal subjects.

Pupillometric findings in patients with Parkinson's disease and cognitive disorder.

The aim of this study is to investigate the changes of the pupil's light reflex (PLR) and mobility in Parkinson's disease (PD) patients with and without cognitive disorder. Twenty two (22) patients (ten males, twelve females, mean age: 72.7+/-7.3 years) with identified PD entered the study. The patients were examined with the Mini Mental State Examination (MMSE), the Wechsler II Memory Scale (WMS II) and the Hamilton Depression Scale (HAM-D17). Eleven (11) patients (five males, six females, mean age: 72.09+/-7.06 years) were free of any cognitive deficits and eleven (11) patients (five males, six females, mean age: 73.36+/-7.55 years) had cognitive disorder according to the aforementioned scales. None of the patients satisfied the DSM-IV-TR criteria for depression or anxiety disorder. The patients underwent a pupillometric study in both eyes with single flash stimuli of 24.6 candelas/m(2) intensity and 20 ms duration. The pupillometric parameters that were studied were: Latency for the onset of Constriction (T1), Baseline Pupil Radius (R1), Minimum Pupil Radius after the pupil reaction to light (R2), Amplitude (AMP, R1-R2), Time for maximum Miosis (T2), Maximum Constriction Velocity (VCmax) and Maximum Constriction Acceleration (ACmax). The pupillometric findings of each group were compared to those of an age and sex matched group of eleven healthy subjects. Furthermore, a comparison between the findings of the two groups was conducted. ACmax and VCmax were significantly lower in patients without (PD) and with coexisting cognitive impairment (PDC) compared to normal subjects (NC) (p<0.001). Patients with cognitive impairment (PDC) had significantly lower levels of ACmax, VCmax and AMP than patients without cognitive deficits (PD). Cognitive impairment in PD, which mainly reflects a central cholinergic deficit, may be a crucial pathogenetic factor for the decrease in the aforementioned pupillometric parameters. VCmax and ACmax can be considered as the most sensitive indicators of this central cholinergic deficiency.