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Objective: The main objective of this research was to evaluate the correlation between the severity of hearing loss and the facial emotional recognition as a critical part of social cognition in elderly patients. Methods: The prospective study was comprised of 85 individuals. The participants were divided into 3 groups. The first group consisted of 30 subjects older than 65 years with a bilateral pure-tone average mean >30 dB HL. The second group consisted of 30 subjects older than 65 years with a PTA mean ≤30 dB HL. The third group consisted of 25 healthy subjects with ages ranging between 18 and 45 years and a PTA mean ≤25 dB HL. A Facial Emotion Identification Test and a Facial Emotion Discrimination Test were administered to all groups. Results: Elderly subjects with hearing loss performed significantly worse than the other 2 groups on the facial emotion identification and discrimination tests ( P Conclusions: Our results suggest that increased age might be associated with decreased facial emotion identification and discrimination scores, which could be deteriorated in the presence of significant hearing loss.

PubMed: 33035413 Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still unclear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-yearold man with lack of generalised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature. © 2020 Ifjusagi Lap-es Konyvkiado Vallalat. All rights reserved.

Introduction: The pre-supplementary motor area (Pre-SMA) plays a pivotal role in the control of voluntary motor control and freezing of gait (FOG) pathophysiological mechanism. Here, we aimed to modulate if the pre-SMA would have beneficial effects on motor and behavioural outcomes in freezing of gait. To test this hypothesis, we examined the left pre-SMA stimulating effect of repetitive Transcranial Magnetic Stimulation (rTMS) on motor, cognitive and behavioural parameters in Parkinson’s patients with FOG. Method: The study included 20 Parkinson’s patients with FOG (3 females, 17 males) who received the left Pre-SMA rTMS procedure. The clinical assessments were performed on all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. Results & Discussion: We found significant improvements in motor, cognitive and behavioural symptoms (p Conclusion: The high-frequency rTMS stimulation over the left preSMA has a restorative effect on the motor, cognitive and behavioural symptoms of Parkinson’s patients with FOG.

ZIRH, Ali/0000-0002-8811-2263 WOS: 000486093600010 PubMed: 31383472 Deep brain stimulation (DBS) is still a highly effective treatment option that significantly improves motor function in advanced PD. Moreover, previous findings have shown that Olfactory dysfunction (OD) has been found in a majority of patients with Parkinson's Disease (PD). Despite this, the effect of DBS on the olfactory function is not fully understood. Here we aimed to determine the effect of STN DBS on OD by evaluating the olfactory functions in the preoperative and postoperative early stages (1st and 3rd months) in forty-five PD patients and 40 healthy controls. The therapeutic effect of DBS on the improvement of motor functions was parallelly investigated. We have observed that there was a significant improvement in OI in the 1st month and in all olfactory parameters (OT, ODI, OI, and TDI) in the 3rd month. In evaluating the motor functional scores, we have revealed a statistically significant (p < 0.001) difference between preoperative UPDRS-motor score (23 +/- 7.3) and the postoperative 3rd month score (11.1 +/- 5.1). Although Beck Depression and Anxiety scores were improved to a certain level in the 3rd month, this improvement was not at a statistically significant level (p > 0.05). As a conclusion, we have shown that STN-DBS improves the smell functions in PD within three months suggesting that the therapeutic effects of DBS might have a wide range of therapeutic spectrum. Despite some limitations (i.e., short follow-up period) our study gives a critical message that future studies are needed to evaluate the functional correlates of STN-DBS treatment in PD patients. (C) 2019 Elsevier Ltd. All rights reserved.

Background Quantitative analysis of the high-resolution T1-weighted images provides useful markers to measure anatomical changes during brain degeneration related to major depressive disorder (MDD). However, there are controversial findings regarding these volume alterations in MDD indicating even to increased volumes in some specific regions in MDD patients. Methods This study is a case-controlled study including 23 depression patients and 15 healthy subject person and 20-38 years of age, who have been treated at the Neurology and Psychiatry Department here. We compared specific anatomic regions between drug-free MDD patients and control group through MRI-Cloud, which is a novel brain imaging method that enables to analyze multiple brain regions simultaneously. Results We have found that frontal, temporal, and parietal hemispheric volumes and middle frontal gyrus, inferior frontal gyrus, superior parietal gyrus, cingulum-hippocampus, lateral fronto-orbital gyrus, superior temporal gyrus, superior temporal white matter, middle temporal gyrus subanatomic regions were significantly reduced bilaterally in MDD patients compared to the control group, while striatum, amygdala, putamen, and nucleus accumbens bilaterally increased in MDD group compared to the control group suggesting that besides the heterogeneity among studies, also comorbid factors such as anxiety and different personal traits could be responsible for these discrepant results. Conclusion Our study gives a strong message that depression is associated with altered structural brain volumes, especially, in drug-free and first-episode MDD patients who present with similar duration and severity of depression while the role of demographic and comorbid risk factors should not be neglected. Alanya Alaaddin Keykubat University

WOS: 000596504400004 PubMed: 33127444 Objectives: Charles Bonnet Syndrome (CBS) is a rare clinical condition which has been defined as complex visual hallucinations (CVH) due to visual loss. This study investigated differences in the EEG power spectral density (PSD) and magnitude-squared coherences between patients with eye disease and hallucinations (VH+), and the control subjects with eye disease without hallucinations (VH-). Methods: 19 scalp channels EEG was recorded in four VH+ (CBS) and four VH- subjects during an eyes-closed resting condition. Artefact-free epochs were analyzed to obtain PSD values in the delta, theta, alpha1, alpha2, beta1, beta2 and gamma frequency bands. Coherence values were calculated through inter-hemispheric and intra-hemispheric electrodes pairs of interest. All subjects were performed with neuropsychological and behavioral assessments to evaluate cognitive functions. Results: The VH + group had increase PSD in theta, beta2 and gamma bands in central, parietal and occipital (O2) areas. The synchronicity was altered particularly in parietal and frontal-parietal regions especially at theta and alpha1 respectively. Conclusions: The aberrant activity in occipital and parietal regions suggest the mechanism of CBS. This is a major electrophysiological study of understanding CBS and visual hallucinations.

Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. Here, we analysed the brain transcriptomics data of more than 600 AD patients using genome-scale metabolic models and provided supporting evidence of mitochondrial dysfunction related to the pathophysiologic mechanisms of AD progression. Subsequently, we investigated, in a rat model of AD, the oral administration of Combined Metabolic Activators (CMA), consisting of NAD+ and glutathione precursors, to explore the effect for improvement of biological functions in AD. CMA includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate, salt form of L-carnitine. The study revealed that supplementation of the CMA improved the AD-associated histological parameters in the animals. Finally, we designed a randomized, double-blinded, placebo-controlled human phase 2 clinical trial and showed that the administration of CMA improves cognitive functions in AD patients. As decreased AD Assessment Scale-cognitive subscale (ADAS-Cog) score is the indicator of the improved cognitive function in AD patients, we observed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (Log2FC= -0.37, (29% improvement), p-value=0.00001) in the CMA group. We also observed a significant decrease in the placebo group on Day 84 vs Day 0 (Log2FC= -0.19, (14% improvement), p-value=0.001) possibly due to the recommendations of exercise and Mediterranean diet to all AD patients and/or a placebo effect apparent in the early stages of AD clinical trials. A comprehensive analysis of the human plasma metabolome and proteome revealed that plasma levels of proteins and metabolites associated with redox metabolism are significantly improved after treatment. In conclusion, our results show that treating AD patients with CMA leads to enhanced cognitive functions, suggesting a role for such a therapeutic regime in treating AD and other neurodegenerative diseases. Funding: This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation. The authors would like to thank the Metabolon Inc. (Durham, USA) for generation of metabolomics data, and ChromaDex Inc. (Irvine, CA, USA) for providing NR. AM and HY acknowledge support from the PoLiMeR Innovative Training Network (Marie Sklodowska-Curie Grant Agreement No. 812616) which has received funding from the European Union’s Horizon 2020 research and innovation programme. Declaration of Interest: AM, JB and MU are the founder and shareholders of ScandiBio Therapeutics. The other authors declare no competing interests. Ethical Approval: All experiments for the treatment of the animals were approved by the Ethics Committee of Ataturk University, and were conducted following the National Institutes of Health Guide for Care and Use of Laboratory Animals.

Cankaya, Seyda/0000-0001-5309-0351 WOS: 000556833000037 PubMed: 32376158 Introduction: Although previous evidence suggest that paracetamol decreases psychological reactivity in healthy subjects, there is still no confirmed correlation between the empathy scores and brain activity in healthy and headache patients after paracetamol treatment. Material and methods: The study group included 16 patients with tension-type headache, and 12 healthy age-and sex-matched controls. After a detailed neurological examination Positive and Negative Affect Schedule (PANAS) and Empathy for Pain Scale (EPS) were applied to all subjects. Next, 1000 mg paracetamol tablet was administered orally, after administration of paracetamol, EPS were repeated, and fMRI was performed to all subjects. Results: We have revealed increased empathy scores in the headache group after the paracetamol treatment which were associated with significant alterations in brain regions which play a critical role in the processing of empathy. Discussion: The observed neuroimaging and clinical difference between healthy and headache subjects could be related to the fact that pain perception in healthy subjects might differ in some aspects from the mechanisms of empathy in headache-experienced patients. Conclusion: To the best of our knowledge, this is the first study that evaluated the paracetamol treatment and neural networks' correlation with pain empathy in healthy and headache individuals. (C) 2020 Elsevier Ltd. All rights reserved.

Background and Aim:Recent data have shown that olfactory dysfunction is strongly related to Alzheimer’s Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes.Methods:We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT).Results:We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction.Conclusion:To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline.

Toprak, Guven/0000-0003-4856-9987; Saricaoglu, Mevhibe/0000-0002-1289-4641 WOS: 000525932300006 PubMed: 32057924 It has been already shown that the motor symptoms of the Parkinson's Disease (PD) have been improved with high frequency rTMS although there is no consensus on the most suitable target brain localization for a maximal therapeutic efficacy. Here, we aimed to compare the therapeutic effect of high frequency (5Hz) rTMS stimulation on primary motor cortex (M1) and pre-supplementary (pre SMA) regions in patients with PD who were still on pharmacological treatment. The study included right-hand dominant16 patients with PD (5 females, 11 males) with demographically and clinically similar characteristics which were randomly assigned to group 1 (n=8) and group 2 (n=8) and received left M1 and the left pre-SMA rTMS procedure, respectively. Total and sequential motor scores of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) were applied to all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. Comparisons of the UPDRS-motor scores between two groups yielded significant improvements after the rTMS on pre-SMA compared to M1 (M1 p=0.14; pre-SMA p=0.01). which were especially significant for the bradykinesia (p=0.04) and axial score related items (p=0.01). This is the first study that shows the effect of rTMS on pre-SMA and it appears to be a promising option in the treatment of PD.

Uysal, Omer/0000-0002-8833-697X; Kilic, Ertugrul/0000-0001-6494-8923; Elibol, Birsen/0000-0002-9462-0862 WOS: 000443177600024 PubMed: 30071285 Sirtuins have gained considerable attention as epigenetic regulators for slowing aging and age-related disorders. The growing association between neurodegeneration and inflammation has led researchers to investigate interactions of sirtuins with inflammatory markers in neurodegenerative diseases. We analyzed SIRT1's association with chronic inflammation in dementia as an age-related neurodegenerative condition through Toll-like receptor 4 (TLR4) and interleukin-7 (IL7) for the first time. In the present study, we observed a significant increase in the level of SIRT1 in patients with all types of dementia. Interestingly, the level of TLR4 protein was significantly lower in only the patients with Alzheimer's disease (AD) compared to the healthy elderly subjects. There was no significant change in the level of IL7 between the diseased and healthy elderly subjects. A significant positive correlation between SIRT1 level and age in healthy elderly subjects was evident according to Pearson's correlation test. However, this correlation was not observed in the dementia patients. Furthermore, the positive correlation between the levels of IL7 and TLR4 in the healthy elderly subjects was absent in the dementia patients. However, there was no direct association between the examined single nucleotide polymorphisms (SNPs) and dementia at the molecular level. According to logistic regression analysis, dementia risk increases 1.16 times due to an increase in the SIRT1 level and 24.23 times due to a decrease in the TLR4 level. Interestingly, a high level in the total antioxidant status (TAS) increases the risk of dementia approximately 33.32 times. Therefore, the current study, for the first time, provides a much better molecular understanding of the interaction between decreasing TLR4 levels and increasing SIRT1 levels in dementia, especially in AD. Furthermore, it highlights the importance of epigenetics in several age-related diseases and suggests that developing novel therapies to prevent or slow down the progression of dementia may support healthy aging.

Background and purpose Anterior cerebral infarct (ACA) infarcts are reported very rare that is due to the compensatory collateral circulation provided by the anterior communicating artery. There are very few studies reporting the long-term follow-up results of ACA infarcts regarding their aetiology, clinical features and prognosis. Most studies reported in the literature vary between several months to one year. Methods A total of 27 patients with ACA infarcts were registered (14 women and 13 men). The mean age of the patients was 68.5 (age range: 45-89 years). Results Bilateral ACA infarcts were reported in four patients (14.8%), right ACA infarct in 11 (40%) patients and left ACA infarct in 12 patients (44%). During the initial examination 15 patients (55.5%) were found to have apathy, 13 patients (48%) had incontinence, nine patients (33.3%) had primitive reflexes, 11 patients (40.7%) had aphasia, while six patients (22.2%) were found to suffer from neglect. At the end of one-year follow-up, five patients (22.7%) were reported to have apathy, 6 patients (27.2%) had incontinence, one patient (4.5%) had primitive reflexes, while one patient (4.5%) was found to have permanent aphasia, and no patients was found to suffer from neglect. Conclusion Here we present our clinical data regarding the aetiology, specific clinical characteristics (including the speech disorders) and prognosis of 27 patients with ACA infarcts during a relatively longer follow-up period (3 months - 30 months) in compared to previous literature. We show that there are differences in the etiological factors of ACA infarcts between the Asian and European communities. Regarding speech disorders which are frequently reported during ACA infarcts, our study results are in agreement with other studies suggesting that this clinical picture is more than a real aphasia and associated with general hypokinesia and reduction in psychomotor activity.

Sleep is an important factor that plays a key role in Alzheimer's disease pathogenesis. However, it is still unclear whether poor-quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in Aβ clearance metabolism. To that end, we discuss possible mechanisms underlying the bidirectional interaction between the sleep deprivation and Aβ clearance pathways.

Guntekin, Bahar/0000-0002-0860-0524 WOS: 000498325100052 PubMed: 31477464 We have evaluated an 82 years old PD patient who has acutely developed VH secondary to acute visual loss that was associated with increased electroencephalographic activity in the gamma range over the parietal, occipital and frontal regions. In this respect, we have tested the therapeutic effect of occipital lobe oriented rTMS application and its electrophysiological correlates that led to significant improvement in the hallucinatory symptomatology of the patient after two weeks. We have revealed that the improved hallucinatory symptoms after rTMS application resolved completely after switching from the pramipexole treatment to L-Dopa indicating that there could be a combined therapeutic effect of L-Dopa and rTMS. Furthermore, Quantitative-Electroencephalography analysis has shown that the therapeutic effects of rTMS and L-Dopa were seen with the improvement of impaired gamma power spectrum. Although the main limitation of this report is that this a single case study and that these findings need to be replicated in a larger sample, e.g., as part of a controlled trial, our present findings help us to enlighten the unknown pathophysiological overlapping between the visual hallucinations in PD and Charles Bonnet Syndrome. Finally, our study revealed increased gamma coherence and power spectrum which is seen with visual hallucinations and improved after the application of 1 Hz rTMS on the occipital lobe. These findings together suggest that rTMS could be used as a therapeutic tool for parkinsonian complex VH and probably due affecting gamma coherence and power spectrum. (C) 2019 Elsevier Ltd. All rights reserved.

Objective Episodic memory impairment and underlying pathophysiology in Parkinson's Disease (PD) is poorly investigated. Formerly, it was thought to be a secondary effect of impairment in fronto-striatal circuit. However, recent studies hypothesized that there is a dual progression of PD and memory loss is possibly related to posterior cortex rather than frontal. To understand the impairment, underlying mechanisms should be investigated. Although consolidation is one of these mechanisms consolidation phase of episodic memory in PD was not investigated yet. Recently accelerated long term forgetting (ALF) phenomenon is emphasized in consolidation researches. Method Here it is evaluated the presence of accelerated long-term forgetting in nondemented PD as a consequence of a deficit in consolidation process. 32 patients and 33 controls participated in the study. Turkish Verbal Memory Process Test (VMPT) was applied to both groups. Delayed recall (DR) scores collected after 30 min, one week and six weeks. Forgetting rates were calculated based on these scores. Results: There was significant difference in DR scores of patients compared to controls in the 30th minute and sixth week. Forgetting rate between 30th minute-1st week did not differ but 1st-6th week was found statistically significant across groups. Conclusions: To the best of our knowledge, this is the first study investigating verbal memory consolidation in PD. Results suggested that impairment is possibly related to the late phase of consolidation of verbal memory in neocortex.

WOS: 000379187900010 PubMed ID: 26943480 Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival. EMBO (European Molecular Biology Organization); Turkish Academy of Sciences (TUBA) This work was supported by EMBO (European Molecular Biology Organization) installation Grant and The Turkish Academy of Sciences (TUBA).

WOS: 000552654000017 PubMed: 32479849 Apart from its well-established therapeutic activity on bipolar disorder and depression, lithium exerts neuroprotective activity upon neurodegenerative disorders, such as traumatic brain injury (TBI). However, the cellular signaling mechanisms mediating lithium's neuroprotective activity and long-term dose- and time-dependent effects on close and remote proximity are largely unknown. Herein, we tested prophylactic and acute effects of lithium (2 mmol/kg) after cold- induced TBI. In both conditions, treatments with lithium resulted in reduced infarct volume and apoptosis. Its acute treatment resulted in the increase of Akt, ERK-1/2 and GSK-3 alpha/beta phosphoylations. Interestingly, its prophylactic treatment instead resulted in decreased phosphorylations of Akt, ERK-1/2, p38, JNK-1 moderately and GSK-3 alpha/beta significantly. Then, we tested subacute (35-day follow-up) role of low (0.2 mmol/kg) and high dose (2 mmol/kg) lithium and revealed that high dose lithium group was the most mobile so the least depressed in the tail suspension test. Anxiety level was assessed by light-dark test, all groups' anxiety levels were decreased with time, but lithium had no effect on anxiety like behavior. When subacute effects of injury and drug treatment were evaluated on the defined brain regions, infarct volume was decreased in the high dose lithium group significantly. In contrast to other brain regions, hippocampal atrophies were observed in both lithium treatment groups, which were significant in the low dose lithium group in both hemispheres, which was associated with the reduced cell proliferation and neurogenesis. Our data demonstrate that lithium treatment protects neurons from TBI. However, long term particularly low-dose lithium causes hippocampal atrophy and decreased neurogenesis. Turkish Academy of Sciences (TUBA)Turkish Academy of Sciences This study was supported by The Turkish Academy of Sciences (TUBA).

Background and Objective: Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear. Methods: In our study, we have scanned three patients with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET. Results: Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18FFDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders. Conclusion: From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory.

Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI. Melatonin treatment reduced infarct volume, which was reversed by PI3K/Akt inhibition. However, PI3K/Akt inhibition did not inhibit melatonin's positive effect on brain swelling and IgG extravasation. Additionally, phosphorylation of mTOR, PTEN, AMPKα, PDK1 and RSK1 were increased, while phosphorylation of 4E-BP1, GSK-3α/β, S6 ribosomal protein were decreased in melatonin treated animals. In addition, melatonin decreased apoptosis through reduced p53 phosphorylation by the PI3K/Akt pathway. In conclusion, we demonstrated the activation profiles of PI3K/Akt signaling pathway components in the pathophysiological aspect of ischemic stroke and melatonin's neuroprotective activity. Our data suggest that Akt phosphorylation, preferably at the Thr308 site of the activation loop via PDK1 and PTEN, mediates melatonin's neuroprotective activity and increased Akt phosphorylation leads to reduced apoptosis., Graphical abstract fx1

Thrombolysis is the most effective treatment for acute ischemic stroke representing the basic therapeutic standard in the western world. Novel drug treatments are therefore unlikely to be developed as stand-alone approaches and every novel treatment should be considered as combination treatment together with thrombolysis. Such a combination should exert synergistic actions together with t-PA, and probably even more important decrease the potential adverse effects of thrombolysis including reperfusion-related adverse effects such as cytotoxin and free radical release and toxicity as well as BBB degradation and subsequent hemorrhagic complications. Preclinical data show that this approach can make thrombolysis safer and buy time for later treatment initiation. At current, the clinical evidence for this approach is relatively weak, but a systematic translation of preclinical findings into the human situation is ongoing with some recent hopeful examples from clinical trials.

Background: Lamotrigine and topiramate are well-known agents with their antiepileptic and mood stabilizing effects. Their therapeutic effect is associated with significant alteration of brain metabolism. In our study, we aimed to investigate the neurometabolic correlates of the therapeutic effects of both agents in a depressive patient with anxiety symptoms and cognitive decline. Methods: In addition to structural Cranial Magnetic Resonance Imaging, we also have performed Neuropsychometric evaluation and FDG-PET Brain fludeoxyglucose positron emission tomography (F18) (FDG PET-CT) FDG-PET before and after the treatment. Brain fludeoxyglucose positron emission tomography (F18) (FDG PET-CT) images were taken before and after the treatment using Philips Gemini TF PET/CT equipped with 16 slice CT. The raw FDG-PET data was processed using NeuroQ software (Version 3,5. Syntermed, Inc Atlanta. USA). Results: Topiramate and lamotrigine additively reduced the neuropsychiatric symptoms and test scores which were associated with the improvement of cerebral glucose metabolism. Conclusion: Our present findings support that the therapeutic effect of lamotrigine and topiramate involves a modulatory effect on the glucose metabolism in cortico-subcortical network and suggests the functional role of a bi-directional hippocampal-cingulate connectivity.

WOS: 000395309500007 PubMed ID: 27697039 Background: Charles Bonnet Syndrome (CBS) is a rare clinical condition which is characterized by complex hallucinations in visually impaired patients. The pathophysiology of this disorder remains largely unknown, and there is still no proven treatment for this disease. In our study, we aimed to investigate the neural activity through Electroencephalography (EEG) power and evaluate the effect of rivastigmine in combination with alpha-lipoic acid on hallucination in two CBS patients with diabetic retinopathy. Methods: EEG data was recorded with standard routine EEG protocols for both patients in our electrophysiological research laboratory (REMER Clinical Electrophysiology and Neuromodulation Research and Application Laboratory) with Brain Vision Recorder (Brainproduct, Munich, Germany). All spectral analyses were processed by BrainVision Analyzer 2 (Brainproduct, Munich, Germany, 2.0.4 Version) in 128 Hz sample rates and the EEG recording and analysis was performed before the administration of rivastigmine (4.5 mg/daily and five patch daily for the first and second patients, respectively) in combination with alpha-lipoic acid (600 mg/daily) for both patients while they were not hallucinated during the time period recordings. Based on our measurement protocol, we have compared the patients in the study group with the three control subjects who were found to be normal except of visual disturbances secondary to significant diabetic retinopathy. Results: Highest theta power values were found in right occipital and left temporo-parietal regions for first and second CBS patients, respectively. Additionally, power spectra were lower in two cases as compared to their control groups in the alpha band for all electrodes. We have also shown that acid rivastigmine in combination with alpha-lipoic exerted significant anti-hallucinatory efficiency. Conclusion: Our present findings could support the hypothesis that increased activation of specific areas in the source monitoring system plays an important role in the pathogenesis of CBS. In addition, rivastigmine in combination with alpha-lipoic acid could be a new valuable option for CBS patients.

WOS: 000397116200009 PubMed ID: 27697074 Background: Studies have already shown that hyperglycemia and insulin resistance are significantly associated with the impairment of cerebral glucose metabolism that may secondary lead to cognitive disturbances. In this study, we aimed to evaluate the neurometabolic correlates of diabetes in a patient with Intermittent explosive disorder (IED). Methods: We have investigated the cerebral glucose metabolism via 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts. Results: We have found significantly reduced glucose uptake in left temporoparietal region, pontin area, and left nucleus lentiformis. Discussion: Our present results indicate decreased cerebral glucose metabolism in specific cerebral cortical and subcortical areas. The main limitation of this report is that, this is a single case study and that these findings need to be replicated in well-conducted randomized controlled studies by using additional neuroquantitative methods.

WOS: 000388577100007 Lhermitte-Duclos disease is a rare cerebellar dysplastic gangliocytoma. The most common symptoms include headache, nausea, vomiting, blurred vision, and imbalance. The typical appearance on cranial magnetic resonance imaging is hyper-intensity on T2-weighted images and hypo-intensity on T1-weighted images. The disease generally presents with benign progress. Development of obstructive hydrocephalus is an indication for urgent surgical intervention and surgery outcomes are satisfactory. Orthostatic hypotension is a very rare clinical presentation of this syndrome and ours is the second case of orthostatic hypotension to be reported in the literature. Lhermitte-Duclos hastalığı serebellumun nadir görülen displastik ganliyositomuna verilen isimdir. En sık başvuru şikayetleri baş ağrısı, bulantı, kusma, dengesizlik ve görme bulanıklığıdır. Tanıda kranyal manyetik rezonans görüntülemede T2 ağırlıklı kesitlerde hiperintens, T1 ağırlıklı kesitlerde hipointens görünüm oldukça tipiktir. Sıklıkla iyi seyirlidir. Obstrüktif hidrosefali gelişimi acil cerrahi müdahale endikasyonudur ve sonuç yüz güldürücüdür. Ortostatik hipotansiyon bu sendromun çok nadir görülen klinik prezentasyonu olup bizim hastamız literatürde bildirilen ikinci olgudur.

Background: There is still limited knowledge regarding the role of impaired brain glucose metabolism in the generation of aggression during diabetes. Additionally, there are rapidly replicating piece of evidence suggesting that topiramate may exert significant mood stabilizing effect. In this respect, we aimed to evaluate the neurometabolic correlates of the therapeutic effect of topiramate in a patient with diabetes and Intermittent explosive disorder (IED). Methods: We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts before and after treatment with topiramate. In order to reveal a defined information underlying the improvement of the aggressive symptoms we also combined the PET with Modified Overt Aggression Scale. Results: We have found that topiramate leads to the improvement in Modified Overt Aggression Scale that was well correlated with the increase in cortical brain metabolism. Discussion: The therapeutic role of topiramate may not only suggest secondary deficits due to diminished functions of the cortical part of emotional circuits but also indicate that diabetic individuals may be vulnerable to lower cerebral glucose metabolism in cortical regions. Further clinical trials that include well-conducted randomized controlled trials and cohort studies by using other methods (i.e., magnetic resonance spectroscopy and quantitative EEG analysis) are necessary to confirm our preliminary findings. © 2016 Bentham Science Publishers.

It is widely known that the occurrence of poststroke mood disorders, especially depression, is one of the most frequent complications of stroke.1 Studies evaluating the association of focal lesions with depressive disorder have shown that lesions involving the frontal lobe, caudate, or putamen were more likely to lead to depression than comparable isolated lesions of the brainstem.2,3 To the best of our knowledge, there are no studies in the literature showing the metabolic correlates of poststroke depression that is secondary to an isolated brainstem infarction.

There are rapidly replicating human data suggesting the therapeutic and neurorestorative role of repetitive transcranial magnetic stimulation (rTMS) in clinical depression. However there are only limited experimental studies in the literature and the neurobiological mechanisms of the technique are still unclear. Studies have suggested that modulating of either excitatory or inhibitory neural circuitry may be responsible for the mechanism of action of rTMS while it is still unclear whether rTMS exerts a neuroprotective effect. In the light of these findings, we aimed to review the neuroprotective effect of rTMS in animal models of depression. We have shown that rTMS may exert significant neuroprotective effect through acting on the oxidative injury, stress hormones, dopamine and serotonin levels, Brain Derived Neurotrophic Factor expression, neuroinflamation and hippocampal cell proliferation.

There are rapidly replicating human data suggesting the therapeutic and neurorestorative role of transcranial magnetic stimulation in various neurological and psychiatric disorders. However there are only limited experimental studies in the literature enlighting the neurobiological mechanisms of this technique. In the light of these findings, we aimed to review the neuroprotective effect of rTMS in various animal studies. We have shown that rTMS may exert significant neuroprotective effect through acting on the neuroinflammation, excitotoxicity, oxidative stress and As aggregation.

WOS: 000349331700002 PubMed ID: 25256242 Neuropharmacological relation of religious belief supports the role of dopaminergic activation as the leading neurochemical feature. However, vesicular monoamine transporter-2 (VMAT-2) has been shown to be responsible for removing of neurotransmitters such as dopamine that may secondarily lead to a neuroprotective activity by different neurodegeneration models. Moreover, there are interesting data showing that VMAT-2 may play an important role during religious belief and experience. In the light of these findings, we aimed to review the preclinical and clinical neuroprotective data of Vesicular monoamine transporter (VMAT-2) in different neurodegenerative and neuropsychiatric diseases. In respect of rapidly increasing evidences about the neurobiological and neuroimaging correlates of religious belief, we hypothesized that there is a link between belief and neuroprotection.

The superoxide dismutase 1 (SOD1)G93A mouse was recently established as transgenic model of amyotrophic lateral sclerosis. We were interested to know whether the SOD1 G93A mutation promotes neuronal injury after intraluminal middle cerebral artery thread occlusion and/or retinal ganglion cell (RGC) axotomy in mice, which are highly reproducible and clinically relevant in vivo models of acute and subacute neuronal degeneration, respectively. In our experiments, G93A mutant SOD1 neither influenced ischemic injury after 90 or 30 min of focal ischemia, nor had an impact on the severity of RGC degeneration after optic nerve transection, when human SOD1 G93A mutant mice were compared to human wild-type SOD1 mice. Our data indicate that the clinically relevant SOD1 G93A mutation, which leads to amyotrophic lateral sclerosis in humans and mice, does not necessarily worsen neuronal degeneration in other pathologies. Thus, the G93A mutation may be counterbalanced in non-motor neurons of young animals, and region-specific and age-related factors may be necessary so that neurodegeneration is re-enforced.

Background CBD is a neurodegenerative disorder characterized by asymmetric motor parkinsonism symptomatology and impairment in language, personality and affective functions that are related to frontoparietal atrophy. To date, there is still no effective treatment for CBD. In this respect, TMS may be a novel therapeutic candidate for CBS. Considering all of this evidence, we aimed to evaluate the pre and post-treatment electrophysiological, neurometabolic and neuropsychometric correlates of TMS application in four CBS patients. Methods We have evaluated the pre and post treatment EEG, FDG-PET and detailed clinical behavioral and neuropsychometric test correlates of TMS in four CBD patients who were admitted to our dementia outpatient at the University of Medipol-Istanbul. The following detailed neuropsychometric test procedures were applied to patients; Digit Span (Forward/Back) Test, Verbal Fluency Test, Lexical Fluency Test, Clock Drawing Test, Similarities and Comprehension test, Verbal Learning Test (SBSTTA-Oktem), Wechsler Memory Scale (WMS-Logical Memory Test), Benton Face Recognition Test (BFR), Line Orientation Identification Test (BLOT), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Frontal Behavioral Inventory Test (FBI), Standardized Mini Mental State Examination (MMSE) and Clinical Dementia Rating-Scale (CDR). Results & conclusion We have found that increased pretreatment theta activity was significantly decreased after the TMS treatment in frontal, central and parietal regions that was associated with the normalized glucose metabolism and neurobehavioral test scores after the TMS treatment.

Rifampicin is an antibacterial agent that is widely used in tuberculosis and leprosy therapy. Interestingly, some experimental studies indicate that rifampicin acts as a hydroxyl radical scavenger and a glucocorticoid receptor activator. In this study, the neuroprotective effect of rifampicin was evaluated after transient and permanent focal cerebral ischemia. Anaesthetized mate C57BL/6j mice were submitted to permanent or transient thread occlusion of the middle cerebral artery (MCA). Reperfusion in transient ischemia was initiated 30 min later by thread retraction. Rifampicin or vehicle were applied intraperitoneally before permanent or immediately after 30 min of transient ischemia . Later, 24 It after permanent or transient ischemia, animals were re-anesthetized and decapitated. Brain injury was evaluated by triphenyltetrazolium chloride staining (TTC), terminal transferase biotinylated-dUTP nick end labeling TUNEL and cresyl violet staining. A 20-mg/kg sample of rifampicin showed a significant neuroprotection after cerebral ischemia. The number of TUNEL-positive cells in the striatum, where disseminated tissue injury was observed, was also reduced by application of rifampicin as compared with vehicle-treated animals. The present report shows that administration of rifampicin efficiently reduces brain injury after permanent and transient focal cerebral ischemia in mice. (C) 2003 Elsevier B.V. All rights reserved.

It is well known that multiple sclerosis (MS) is a demyelinating disease of the central nervous system that mostly starts in the second to third decade. In the present study, we reviewed our own observations of the clinical and paraclinical features in the 36 of 890 (4.04%) MS patients whose symptoms started before 16 years of age. The average age at onset of the disease in these 36 patients was 12.9 years. In 18 patients, the disease onset was monosymptomatic. Diplopia and sensory disturbances were the most common initial manifestations and occurred in 27.7% of cases. Twenty-one patients (59%) had a relapsing and 11 patients (30.5%) had a secondary progressive course. On the last evaluation, the EDSS score was above 5 in 11 patients and it was below 5 in 21 patients. As a result of this study, we concluded that childhood onset MS does not significantly differ from that it has been typically seen in adults in terms of major clinical manifestations and course of disease. (C) 2003 Elsevier Science B.V. All rights reserved.