Morphological and morphometric changes in the Purkinje cells of patients with essential tremor.

Essential tremor (ET) is a progressive neurological syndrome characterised by involuntary tremors of the hands or arms, head, jaw and voice. The pathophysiology of ET is not clearly understood yet. However, previous studies have reported several changes in the brain of patients with ET. One of the brain areas extensively investigated is the cerebellum. In the present study, a morphometric analysis of Purkinje cells in patients with ET and ET-plus was performed, and subsequently compared with normal controls using the Golgi silver staining method and 3D neuronal reconstruction. Substantial morphological changes were uncovered in the Purkinje cells of patients with ET compared with normal controls, including a decreased dendritic length and field density, an overall loss of terminal branches and a decreased density of dendritic spines.

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.

Temporal trends in stroke incidence and case-fatality rates in Arcadia, Greece: A sequential, prospective, population-based study.

BACKGROUND: Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies. AIMS: The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece. METHODS: All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015-2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method. RESULTS: In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231-239) in 1993/1995, 252 (95% CI 223-286) in 2004, and 211 (192-232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72-0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58-0.90). CONCLUSIONS: This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016.

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.

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.

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.

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.

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.

A meta-analysis on RT-QuIC for the diagnosis of sporadic CJD.

Creutzfeld-Jakob disease (CJD) is a fatal neurodegenerative disease which belongs to the family of transmissible spongiform encephalopathies (TSEs), or prion diseases. Historically, CJD diagnosis has been based on the combination of clinical features and in vivo markers, including CSF protein assays, MRI and EEG changes. Brain-derived CSF proteins, such as 14-3-3, t-tau and p-tau have been largely used to support the diagnosis of probable CJD, although with certain limitations concerning sensitivity and specificity of these tests. More recently, a new method for the pre-mortem diagnosis of sporadic CJD has been developed, based on the ability of PrPsc to induce the polymerization of protease-sensitive recombinant PrP (PrPsen) into amyloid fibrils, and is known as Real-Time Quaking- Induced Conversion (RT-QuIC) assay allows the detection of > 1 fg of PrPsc in diluted CJD brain homogenate and a variety of biological tissues and fluids. In the present study, we did a meta-analysis on the liability of RT-QuIC method in the diagnosis of sporadic CJD, in comparison to 14-3-3 and Tau protein. Twelve studies were finally included in the statistical analysis which showed that RT-QuIC has a very high specificity and comparable sensitivity to 14-3-3 protein and Tau protein in the CSF, and hence can be used as a reliable biomarker for the diagnosis of sporadic CJD.

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.

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.

Electroencephalogram in dementia with Lewy bodies: a systematic review.

Dementia with Lewy bodies (DLB) belongs to the spectrum of Lewy body dementia (LBD) that also encompasses Parkinson's disease dementia (PDD). It is a common neurodegenerative disorder characterized by memory decline, cognitive fluctuations, visual hallucinations, autonomic nervous system disturbance, REM sleep behavior disorder, and parkinsonism. Definite diagnosis can be established only through neuropathological confirmation of Lewy bodies' presence in brain tissue. Probable or possible diagnosis relies upon clinical features, imaging, polysomnography, and electroencephalogram (EEG) findings. Potential neurophysiological biomarkers for the diagnosis, management, and evaluation of treatment-response in DLB should be affordable and widely available outside academic centers. Increasing evidence supports the use of quantitative EEG (qEEG) as a potential DLB biomarker, with promising results in discriminating DLB from other dementias and in identifying subjects who are on the trajectory to develop DLB. Several studies evaluated the diagnostic value of EEG in DLB. Visual analysis and qEEG techniques have been implemented, showing a superiority of the last in terms of sensitivity and objectivity. In this systematic review, we attempt to provide a general synthesis of the current knowledge on EEG application in DLB. We review the findings from original studies and address the issues remaining to be further clarified.

Spontaneous Epidural Hematomas due to Cerebral Venous Thrombosis in a Patient with Immune Thrombocytopenic Purpura.

INTRODUCTION: Intracerebral haemorrhage in patients suffering from cerebral venous thrombosis (CVT) is relatively uncommon. CVT typically occurs in hypercoagulable state of various causes. Some drugs play a causative role in CVT and thrombopoietin receptor agonists are among them. CASE SUMMARY: We present a female patient with refractory immune thrombocytopenic purpura (ITP) treated with romiplostim, suffering from severe thrombosis of jugular vein expanding intracranially. Despite being treated with adequate anticoagulation, she developed spontaneous bilateral epidural and subdural hematomas with devastating outcome. DISCUSSION: To our knowledge, this is the first reported case of spontaneous atraumatic epidural hematomas due to CVT in adult patient. We support that in our patient, blood stasis leading to the dissection of dura mater, platelet dysfunction, and anticoagulation treatment contributed to the formation of the intracranial, extracerebral haemorrhages.