A meta-analysis on the levels of VILIP-1 in the CSF of Alzheimer's disease compared to normal controls and other neurodegenerative conditions.

Alzheimer's disease (AD) is a progressing neurodegenerative disorder and the main cause of serious irreversible cognitive decline in elderly people. Visinin-like protein 1 (VILIP-1) is a member of the family of calcium-binding proteins and plays a crucial role in AD pathophysiology. Multiple studies have shown that CSF levels of VILIP-1 are increased in AD patients compared to normal controls, or other neurodegenerative conditions. We searched online databases for studies on the levels of VILIP-1 in the CSF of AD patients in comparison to normal controls, mild cognitive impairment (MCI) patients and Dementia with Lewy bodies (DLB) patients. A total of ten studies were used for the comparison between AD and controls, three studies for the comparison between AD and MCI, two studies for AD and DLB and two studies for the comparison between stable MCI and MCI progressed to AD. We found that VILIP-1 levels are significantly higher in AD compared to normal controls, but not to the other groups, and furthermore, they are significantly higher in patient with MCI progressed to AD, than in stable MCI patients.

The role of neurofilament light chain in frontotemporal dementia: a meta-analysis.

Frontotemporal dementia (FTD) is the second most frequent dementia, after Alzheimer's, in patients under the age of 65. It encompasses clinical entities characterized by behavioral, language, and executive control dysfunction. Neurofilament light chain (NfL) is a new, non-disease specific, widely studied biomarker indicative of axonal injury and degeneration. Various studies have previously explored the role of NfL in the diagnostic process, monitoring, and prognosis of dementia. The current systematic review and meta-analysis include all the available data concerning the role of NfL in frontotemporal dementia and its use as a potential biomarker in differentiating patients with FTD from (a) healthy individuals, (b) Alzheimer's dementia, (c) Dementia with Lewy bodies, (d) Motor Neuron disease, (e) Parkinsonian syndromes, and (f) psychiatric disorders. We also analyze the utility of NfL in distinguishing specific FTD subgroups. Neurofilament light chain has a potential role in differentiating patients with frontotemporal dementia from healthy controls, patients with Alzheimer's dementia, and psychiatric disorders. Higher NfL levels were also noted in patients with semantic primary progressive aphasia (PPA) when compared with behavioral FTD and non-fluent PPA patients. Further studies exploring the use of NfL in frontotemporal dementia are needed.

Cognitive Status Epilepticus: Two Case Reports.

Cognitive status epilepticus is an uncommon form of focal status epilepticus presenting with a dysfunction of language, thinking or associated higher cortical functions. The absence of ictal manifestations can be misleading and delay a prompt diagnosis. Here we present two patients; one with amnesic and one with aphasic status epilepticus. Through these cases, we aim to highlight the value of EEG performance early in the diagnostic work-up and early antiepileptic drug initiation in cases where an epileptic disorder cannot be excluded.

A Voxel-Wise Meta-Analysis on the Cerebellum in Essential Tremor.

Background and Objectives: Essential tremor is a chronic progressive neurological condition. The clinical presentation of essential tremor is heterogeneous and includes involuntary tremor on hands or arms and progressively on head, jaw, and voice. More extensive and complex symptoms may also be noticed in several patients. Many studies have been carried out to identify biomarkers to help the diagnosis, however, all the efforts have not shown any substantial results yet. Materials and Methods: Here, we aimed to perform a voxel-based meta-analysis using a dedicated cerebellar mask to clarify whether the results from the previous studies are robust and have any clinical significance. We included studies with a total of 377 essential tremor patients and 338 healthy control individuals. Results: A significant regional decrease in the volume of the gray matter was detected in the right cerebellar hemispheric lobule IV/V, and in the cerebellar vermic lobule IV/V. Conclusions: This is the first study focused on the cerebellum and using a specific cerebellar mask, which increases the sensitivity. It showed regional statistically significant changes that could not be seen in the whole-brain analysis.

Gray Matter Changes in Juvenile Myoclonic Epilepsy. A Voxel-Wise Meta-Analysis.

Background and Objectives. Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epileptic syndrome, with a genetic basis clinically identified by myoclonic jerks of the upper limbs upon awaking, generalized tonic-clonic seizures and less frequent absences. Although the brain magnetic resonance imaging (MRI) is by definition normal, computer-based Voxel-Based morphometry studies have shown a number of volumetric changes in patients with juvenile myoclonic epilepsy. Thus, the aim of the present Voxel-Wise Meta-Analysis was to determine the most consistent regional differences of gray matter volume between JME patients and healthy controls. Materials and Methods. The initial search returned 31 studies. After excluding reviews and studies without control groups or without detailed peak coordinates, 12 studies were finally included in the present meta-analysis. The total number of JME patients was 325, and that of healthy controls was 357. Results. Our study showed a statistically significant increase of the gray matter in the left median cingulate/paracingulate gyri, the right superior frontal gyrus, the left precentral gyrus, the right supplementary motor area and left supplementary motor area. It also showed a decrease in the gray matter volume in the left thalamus, and in the left insula. Conclusions. Our findings could be related to the functional deficits and changes described by previous studies in juvenile myoclonic epilepsy. In this way, the volumetric changes found in the present study could be related to the impaired frontal lobe functions, the emotional dysfunction and impaired pain empathy, and to the disrupted functional connectivity of supplementary motor areas described in JME. It additionally shows changes in the volume of the left thalamus, supporting the theory of thalamocortical pathways being involved in the pathogenesis of juvenile myoclonic epilepsy.

YKL-40 as a Potential Biomarker for the Differential Diagnosis of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, associated with extensive neuronal loss, dendritic and synaptic changes resulting in significant cognitive impairment. An increased number of studies have given rise to the neuroinflammatory hypothesis in AD. It is widely accepted that AD brains show chronic inflammation, probably triggered by the presence of insoluble amyloid beta deposits and neurofibrillary tangles (NFT) and is also related to the activation of neuronal death cascade. In the present study we aimed to investigate the role of YKL-40 levels in the cerebrospinal fluid (CSF) in the diagnosis of AD, and to discuss whether there are further potential roles of this protein in the management and treatment of AD. We conducted an online search on PubMed, Web of Science, and the Cochrane library databases from 1990 to 2021. The quantitative analysis showed that the levels of YKL-40 were significantly higher in Alzheimer's disease compared to controls, to mild cognitive impairment (MCI) AD (MCI-AD) and to stable MCI. They were also increased in MCI-AD compared to stable MCI. The present study shows that the CSF levels of YKL-40 could be potentially used as a biomarker for the prognosis of mild cognitive impairment and the likelihood of progression to AD, as well as for the differential diagnosis between AD and MCI.

Serum BDNF Levels in Acute Stroke: A Systematic Review and Meta-Analysis.

Background and objectives: Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins. Low BDNF concentrations have been noted in patients with traditional cardiovascular disease risk factors and have been associated with the increased risk of stroke/transient ischemic attack (TIA). We aimed to study the correlation of BDNF serum levels with acute stroke severity and its potential role as a biomarker in predicting functional outcome. Materials and methods: We systematically searched PubMed, Web of Science, and the Cochrane database using specific keywords. The endpoints examined were the correlation of BDNF with functional outcome, the National Institute of Health stroke scale (NIHSS) measured at the acute phase, and stroke infarct volume. We also compared serum BDNF levels between stroke patients and healthy controls. Results: Twenty-six records were included from the initial 3088 identified. Twenty-five studies reported NIHSS and BDNF levels on the first day after acute stroke. Nine studies were further meta-analyzed. A statistically significant negative correlation between NIHSS and BDNF levels during the acute phase of stroke was noted (COR: -0.3013, 95%CI: (-0.4725; -0.1082), z = -3.01, p = 0.0026). We also noted that BDNF levels were significantly lower in patients with stroke compared to healthy individuals. Due to the heterogeneity of studies, we only conducted a qualitative analysis regarding serum BDNF and functional outcome, while no correlation between BDNF levels and stroke infarct volume was noted. Conclusions: We conclude that in the acute stroke phase, stroke severity is negatively correlated with BDNF levels. Concurrently, patients with acute stroke have significantly lower BDNF levels in serum compared to healthy controls. No correlations between BDNF and stroke infarct volume or functional outcome at follow-up were noted.

Alpha-synuclein Levels in the Differential Diagnosis of Lewy Bodies Dementia and Other Neurodegenerative Disorders: A Meta-analysis.

SUBJECTIVES: Lewy body dementia (LBD) is the second most common type of neurodegenerative dementia after Alzheimer disease (AD). It is characterized by the accumulation of Lewy bodies and Lewy neurites which are composed of aggregated phosphorylated alpha-synuclein, which is a presynaptic neuronal protein genetically and neuropathologically linked to Parkinson disease and to LBD. Alpha-synuclein is thought to contribute to LBD pathogenesis and to linked to disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including synaptic function. METHODS: In the present study, we did a meta-analysis on the reliability of alpha-synuclein levels in the cerebrospinal fluid (CSF) for the discrimination between LBD and other neurodegenerative disorders including AD, Parkinson disease (PD) dementia, progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and frontotemporal dementia (FTD). RESULTS: CSF alpha-synuclein levels were significantly different in LBD compared with AD, but no statistical difference was found between LBD, and dementia in PD, MSA, PSP, and FTD. CONCLUSION: Alpha-synuclein levels in the CSF can be used for the discrimination between LBD and AD, but not LBD and other neurodegenerative disorders such as dementia in PD, MSA, FTD, and PSP.

A meta-analysis on CSF neurogranin levels for the diagnosis of Alzheimer's disease and mild cognitive impairment.

OBJECTIVE: Neurogranin is a postsynaptic protein involved in long-term potentiation and synaptic plasticity. Recent studies have shown increased neurogranin levels in the cerebrospinal fluid of Alzheimer's disease patients, and in patients with mild cognitive impairment. METHOD: We searched the online databases for studies on neurogranin cerebrospinal fluid levels in Alzheimer's disease, mild cognitive impairment and other neurodegenerative disorders, and we did a meta-analysis to clarify whether this can be a reliable biomarker for the diagnosis of Alzheimer's disease, and the discrimination from other disorders. RESULTS: The present meta-analysis showed that neurogranin CSF levels are significantly higher in AD patients compared to NC [SMD: 268.26, 95% CI (143.47, 393.04), Z = 4.21, P = 0.0001], MCI [SMD: 23.45 (15.97, 30.92), Z = 6.15, P < 0.00001], FTD [SMD: 1.91 (0.92, 2.89), Z = 3.80, P < 0.0001], but no significant difference was found between AD and LBD [SMD: 138.51 (- 14.92, 291.95), Z = 1.77, P = 0.08]. Comparison of stable MCI and MCI that progressed to AD showed significantly higher levels in the CSF of MCI patients who progressed to AD, compared to stable MCI patients [SMD: 230.84 (12.54, 449.14), Z = 2.07, P = 0.04]. Neurogranin can also be a useful biomarker for the differentiation MCI and NC, but not between MCI and FTD or LBD. CONCLUSION: Neurogranin could be added to the panel of existing biomarkers for a more accurate diagnosis and progress of AD and assessment of underlying pathological changes in the brain.

A review of the personality traits in post-concussion syndrome.

INTRODUCTION: Various manifestations ranging from physical symptoms to cognitive and emotional impairments could often be seen following head concussions that lead to mild traumatic brain injury (mTBI). These symptoms are commonly comprising the post-concussion syndrome (PCS) and their resolution could be influenced by multiple factors. Personality traits have been suggested as potential risk factors for the emergence and persistence of PCS. In this study, we aimed to investigate the possible predisposition to PCS given by certain personality traits. METHODS: Prospective cohort studies, observational studies, and cross-phenotype polygenic risk score analyses were selected from the main scientific databases (PubMed/Medline, Scopus, EMBASE, Web of Science) based on multiple-step screening, using keywords (such as "personality traits", "post-concussion syndrome", "traumatic brain injury", "anxiety", "depression", "resilience", and "somatization") and inclusion/exclusion criteria (English written studies available in full text presenting relevant data on TBI patients and their personality traits; reviews, animal studies, and studies not written in English, not available in full text, or not presenting full demographical and clinical data were excluded). The investigated personality traits included emotional reserve, somatic trait anxiety, embitterment, mistrust, parental anxiety, state anxiety, trait anxiety, anxiety sensitivity, pain catastrophizing, helplessness, sports-concussion symptom load, and cognitive resilience. RESULTS: The reviewed data from 16 selected studies suggested that personality traits play an essential role in the development and persistence of PCS. Emotional reserve, cognitive resilience, and lower levels of somatic trait anxiety were associated with better outcomes in PCS. However, higher levels of anxiety sensitivity, pain catastrophizing, helplessness, and sports-concussion symptom load were associated with worse outcomes in PCS. Parental anxiety was not associated with persistent symptoms in children following concussion. Despite the statistical analysis regarding the included publications bias was low, further studies should further investigate the correlation between TBI and some personality traits, as some of the selected studies did not included healthy individuals and their psychological profiles for comparison and correlation analysis. CONCLUSION: Personality traits may help predict the development and persistence of PCS following mTBI. Understanding the personality traits roles in PCS could assist the development of targeted interventions for the prevention and treatment of PCS. Further research is needed to better understand the complex interactions between personality traits, neurobiological factors, and psychosocial factors in PCS.

Epidemiology, Risk Factors, and Biomarkers of Post-Traumatic Epilepsy: A Comprehensive Overview.

This paper presents an in-depth exploration of Post-Traumatic Epilepsy (PTE), a complex neurological disorder following traumatic brain injury (TBI), characterized by recurrent, unprovoked seizures. With TBI being a global health concern, understanding PTE is crucial for effective diagnosis, management, and prognosis. This study aims to provide a comprehensive overview of the epidemiology, risk factors, and emerging biomarkers of PTE, thereby informing clinical practice and guiding future research. The epidemiological aspect of the study reveals PTE as a significant contributor to acquired epilepsies, with varying incidence influenced by injury severity, age, and intracranial pathologies. The paper delves into the multifactorial nature of PTE risk factors, encompassing clinical, demographic, and genetic elements. Key insights include the association of injury severity, intracranial hemorrhages, and early seizures with increased PTE risk, and the roles of age, gender, and genetic predispositions. Advancements in neuroimaging, electroencephalography, and molecular biology are presented, highlighting their roles in identifying potential PTE biomarkers. These biomarkers, ranging from radiological signs to electroencephalography EEG patterns and molecular indicators, hold promise for enhancing PTE pathogenesis understanding, early diagnosis, and therapeutic guidance. The paper also discusses the critical roles of astrocytes and microglia in PTE, emphasizing the significance of neuroinflammation in PTE development. The insights from this review suggest potential therapeutic targets in neuroinflammation pathways. In conclusion, this paper synthesizes current knowledge in the field, emphasizing the need for continued research and a multidisciplinary approach to effectively manage PTE. Future research directions include longitudinal studies for a better understanding of TBI and PTE outcomes, and the development of targeted interventions based on individualized risk profiles. This research contributes significantly to the broader understanding of epilepsy and TBI.

Neurofilament light chain in patients with a concussion or head impacts: a systematic review and meta-analysis.

PURPOSE: Traumatic brain injury is one of the leading causes of disability worldwide. Mild traumatic brain injury (TBI) is the most common and benign form of TBI, usually referred to by the medical term "concussion". The purpose of our systematic review and meta-analysis was to explore the role of serum and CSF neurofilament light chain (NfL) as a potential biomarker in concussion. METHODS: We systematically searched PubMed, Web of Science, and Cochrane databases using specific keywords. As the primary outcome, we assessed CSF or serum NfL levels in patients with concussion and head impacts versus controls. The role of NfL in patients with concussion and head impacts compared to healthy controls was also assessed, as well as in sports-related and military-related conditions. RESULTS: From the initial 617 identified studies, we included 24 studies in our qualitative analysis and 14 studies in our meta-analysis. We found a statistically significant increase of serum NfL in patients suffering from a concussion or head impacts compared to controls (p = 0.0023), highlighting its potential role as a biomarker. From our sub-group analyses, sports-related concussion and mild TBI were mostly correlated with increased serum NfL values. Compared to controls, sports-related concussion was significantly associated with higher NfL levels (p = 0.0015), while no association was noted in patients suffering from head impacts or military-related TBI. CONCLUSION: Serum NfL levels are higher in all patients suffering from concussion compared to healthy controls. The sports-related concussion was specifically associated with higher levels of NfL. Further studies exploring the use of NfL as a diagnostic and prognostic biomarker in mild TBI and head impacts are needed.

Diagnostic Accuracy of Anti-CN1A on the Diagnosis of Inclusion Body Myositis. A Hierarchical Bivariate and Bayesian Meta-analysis.

ABSTRACT: Sporadic inclusion body myositis (IBM) is an acquired muscle disease and the most common idiopathic inflammatory myopathy over the age of 50. It is characterized by male predominance, with a prevalence rate between 1 and 71 cases per million, reaching 139 cases per million over the age of 50 globally. The diagnosis of IBM is based on clinical presentation and muscle biopsy findings. However, there is increasing evidence for the role of genetics and serum biomarkers in supporting a diagnosis. Antibodies against the cytosolic 5'-nucleotidase 1A (Anti-CN1A), an enzyme catalyzing the conversion of adenosine monophosphate into adenosine and phosphate and is abundant in skeletal muscle, has been reported to be present in IBM and could be of crucial significance in the diagnosis of the disease. In this study, we investigated the diagnostic accuracy of anti-CN1A antibodies for sporadic IBM in comparison with other inflammatory myopathies, autoimmune disorders, motor neurone disease, using a hierarchical bivariate approach, and a Bayesian model taking into account the variable prevalence. The results of the present analysis show that anti-CN1A antibodies have moderate sensitivity, and despite having high specificity, they are not useful biomarkers for the diagnosis of IBM, polymyositis or dermatomyositis, other autoimmune conditions, or neuromuscular disorders. Neither the hierarchical bivariate nor the Bayesian analysis showed any significant usefulness of anti-CN1A antibodies in the diagnosis of IBM.

Morphological alterations of the pyramidal and stellate cells of the visual cortex in schizophrenia.

Schizophrenia is a severe brain disorder characterized by certain types of delusion, hallucination and thought disorder. Studies have revealed impaired synaptic plasticity and reduced gamma-aminobutyric acid levels of the visual cortex in patients with schizophrenia. While previous work established a critical role for interneurons and cortical connectivity in the generation of hallucinations, the present study set out to examine the morphology of pyramidal cells and interneurons from layers 3 and 4 in the primary visual cortex from schizophrenic brains and to identify any dendritic and spinal alterations in comparison to normal control brains. The morphological and morphometric changes of the pyramidal cells and the interneurons of the visual cortices of 10 brains obtained from patients with schizophrenia, in comparison to 10 age-matched controls, were studied using the Golgi method and 3D neuronal reconstruction techniques. Analysis using the Golgi impregnation technique revealed a significant loss of distal dendritic segments, tortuous branches and varicosities and an overall restriction of the dendritic field in the brains of schizophrenic patients in both pyramidal cells and in aspiny interneurons. The present results may explain certain clinical phenomena associated with the visual cortex usually encountered in schizophrenia.