Biosensors, Recent Advances in Determination of BDNF and NfL.

Key biomarkers such as Brain Derived Neurotrophic Factor (BDNF) and Neurofilament light chain (NfL) play important roles in the development and progression of many neurological diseases, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In these clinical conditions, the underlying biomarker processes are markedly heterogeneous. In this context, robust biomarker discovery is of critical importance for screening, early detection, and monitoring of neurological diseases. The difficulty of directly identifying biochemical processes in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory response have been identified in various body fluids such as blood, cerebrospinal fluid, and tears. Furthermore, biotechnology and nanotechnology have facilitated the development of biosensor platforms capable of real-time detection of multiple biomarkers in clinically relevant samples. Biosensing technology is approaching maturity and will be deployed in communities, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight clinical and current technological advances in the development of multiplex-based solutions for effective diagnosis and monitoring of neuroinflammatory and neurodegenerative diseases. The trend in the detection if BDNF and NfL.

Psychometric properties of the Persian version of the Patient-Weighted Quality of Life in Epilepsy Inventory-10-P.

BACKGROUND: The purpose of the study was to evaluate psychometric properties of the Persian version of the Patient-Weighted Quality of Life in Epilepsy Inventory-10-P (PV QOLIE-10-P). METHODS: The Persian version was obtained from the original version by standard forward/backward translation. We assessed content validity, construct validity by factor analysis, internal consistency, test-retest reliabilities, criterion validity by calculating Pearson/Spearman correlation to the Persian version of the SF-36 inventory the Persian version of the 36-Item Short Form Health Survey (PV SF-36), and discriminant validity by calculating Pearson/Spearman correlation to demographic features and epilepsy-specific characteristics. RESULTS: One hundred and fifty-five adult patients with epilepsy were enrolled in the study. The 10 items of PV QOLIE-10-P were grouped into two factors: epilepsy effects/role function scale (driving, work, social, memory, physical effect, and mental effect) and mental health scale (energy, depression, seizure worry, and overall quality of life). The Cronbach's alpha value was 0.859. Test-retest analysis revealed statistically significant correlations for total score and the scales (correlation coefficient for total score, epilepsy effects/role function, and mental health were 0.7, 0.66 and 0.7respectively). The Pearson correlation coefficient between total scores of the Persian version of QOLIE10-P and SF-36 was 0.822 (p < 0.001). The PV QOLIE-10-P was able to differentiate patients with marriage, education, job, seizure type, seizure frequency, and antiepileptic treatment. CONCLUSION: The Persian version of QOLIE-10-P is a valid and reliable tool to assess the quality of life of patients with epilepsy in Iran.

Stem cell-based cell therapy for neuroprotection in stroke: A review.

Neurological disorders, such as stroke, are triggered by a loss of neurons and glial cells. Ischemic stroke remains a substantial problem for industrialized countries. Over the previous few decades our understanding about the pathophysiology of stroke has enhanced, nevertheless, more awareness is required to advance the field of stroke recovery. Existing therapies are incapable to adequately relief the disease outcome and are not appropriate to all patients. Meanwhile, the majority of patients continue to show neurological deficits even subsequent effective thrombolysis, recuperative therapies are immediately required that stimulate brain remodeling and repair once stroke damage has happened. Cell therapy is emergent as a hopeful new modality for increasing neurological recovery in ischemic stroke. Numerous types of stem cells from various sources have been identified and their possibility and efficiency for the treatment of stroke have been investigated. Stem cell therapy in patients with stroke using adult stem cells have been first practiced in clinical trials since 15 years ago. Even though stem cells have revealed a hopeful role in ischemic stroke in investigational studies besides early clinical pilot studies, cellular therapy in human is still at a primary stage. In this review, we summarize the types of stem cells, various delivery routes, and clinical application of stem cell-based therapy for stroke treatment.

Parkinson Disease from Mendelian Forms to Genetic Susceptibility: New Molecular Insights into the Neurodegeneration Process.

Parkinson disease (PD) is known as a common progressive neurodegenerative disease which is clinically diagnosed by the manifestation of numerous motor and nonmotor symptoms. PD is a genetically heterogeneous disorder with both familial and sporadic forms. To date, researches in the field of Parkinsonism have identified 23 genes or loci linked to rare monogenic familial forms of PD with Mendelian inheritance. Biochemical studies revealed that the products of these genes usually play key roles in the proper protein and mitochondrial quality control processes, as well as synaptic transmission and vesicular recycling pathways within neurons. Despite this, large number of patients affected with PD typically tends to show sporadic forms of disease with lack of a clear family history. Recent genome-wide association studies (GWAS) meta-analyses on the large sporadic PD case-control samples from European populations have identified over 12 genetic risk factors. However, the genetic etiology that underlies pathogenesis of PD is also discussed, since it remains unidentified in 40% of all PD-affected cases. Nowadays, with the emergence of new genetic techniques, international PD genomics consortiums and public online resources such as PDGene, there are many hopes that future large-scale genetics projects provide further insights into the genetic etiology of PD and improve diagnostic accuracy and therapeutic clinical trial designs.

Association Between the Endocannabinoid System-Related Gene Variants and Epilepsy.

The endocannabinoid system (ECS) is an intricate network consisting of receptors, enzymes, and endogenous ligands that play a pivotal role in various neurological processes. It has been implicated in the pathophysiology of several neurological disorders, including epilepsy. Extensive research has demonstrated the involvement of genetic factors in influencing the susceptibility to and progression of epilepsy. In this study, we focused on investigating the connection between genetic variations in genes related to the ECS and the occurrence of epilepsy. Some ECS-related gene variants were selected and genotyping was performed using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Interestingly, CNR1 rs12720071 genotype (OR 16.33, 95% CI 1.8-149; p = 0.001) showed an association with generalized epilepsy and MGLL rs604300 genotype (OR 2, 95% CI 1.1-3.4; p = 0.013) demonstrated a relationship with females diagnosed with focal epilepsy. So, studying CNR1, MGLL, and their genetic variations provides insights into the role of the endocannabinoid system in health and diseases. Moreover, they hold the potential to pave the way for the development of novel therapeutic approaches specifically targeting them.

The study of rs324420 (C385A) polymorphism of the FAAH gene of the endocannabinoid system in patients with epilepsy and ADHD.

The endocannabinoid (eCB) system regulates many physiological functions in the central nervous system. Fatty acid amide hydrolase (FAAH) is an essential enzyme in the eCB system, degrading anandamide. Single nucleotide polymorphism (SNP) rs324420 is a common genetic polymorphism of the FAAH gene and has been associated with susceptibility to neurological conditions. This study examined whether the SNP rs324420 (C385A) is associated with epilepsy and attention deficit hyperactivity disorder (ADHD). This study consists of two case-control parts. The first part comprises 250 epilepsy subjects and 250 healthy individuals as controls. The second one comprises 157 cases with ADHD and 136 healthy individuals as controls. Genotyping was carried out using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Interestingly, the FAAH C384A genotype (OR 1.755, 95 % CI 1.124-2.742, p = 0.013) and allele (OR 1.462, 95 % CI 1.006-2.124, p = 0.046) distribution showed an association with generalized epilepsy. On the other hand, this SNP was not associated with the risk of ADHD. To our knowledge, there was no study on the association between rs324420 (C385A) polymorphism and the risks of ADHD or epilepsy. This study provided the first evidence of an association between generalized epilepsy and rs324420 (C385A) of FAAH. Larger sample sizes and functional studies are warranted to explore the clinical utility of FAAH genotyping as a possible marker for increased generalized epilepsy risk.

Biosensors technology for anti-epileptic drugs.

A broad group of antiepileptic drugs (AEDs) often controls the frequency of seizures. Given the variability of pharmacokinetics, narrow target range, and the difficulty of identifying signs of toxicity from laboratory responses, therapeutic monitoring of AEDs plays a vital role in optimizing drug administration. Nanomaterials, especially biosensor-based methods, can facilitate the analysis of these agents with unique advantages such as rapid analysis, sensitivity, selectivity, and low cost. This review describes recent advances in biosensors developed to analyze AEDs. First, we described common electrochemical measurement techniques and types of deposited electrode substrates. Additionally, various chemical and biological modifiers to improve the sensitivity and selectivity of the sensor have been categorized and briefly described. Finally, the prospects for developing an electrochemical platform for quantifying AEDs are presented.

Molecular insights into the role of AMPA receptors in the synaptic plasticity, pathogenesis and treatment of epilepsy: therapeutic potentials of perampanel and antisense oligonucleotide (ASO) technology.

Glutamate is considered as the predominant excitatory neurotransmitter in the mammalian central nervous systems (CNS). Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the main glutamate-gated ionotropic channels that mediate the majority of fast synaptic excitation in the brain. AMPARs are highly dynamic that constitutively move into and out of the postsynaptic membrane. Changes in the postsynaptic number of AMPARs play a key role in controlling synaptic plasticity and also brain functions such as memory formation and forgetting development. Impairments in the regulation of AMPAR function, trafficking, and signaling pathway may also contribute to neuronal hyperexcitability and epileptogenesis process, which offers AMPAR as a potential target for epilepsy therapy. Over the last decade, various types of AMPAR antagonists such as perampanel and talampanel have been developed to treat epilepsy, but they usually show limited efficacy at low doses and produce unwanted cognitive and motor side effects when administered at higher doses. In the present article, the latest findings in the field of molecular mechanisms controlling AMPAR biology, as well as the role of these mechanism dysfunctions in generating epilepsy will be reviewed. Also, a comprehensive summary of recent findings from clinical trials with perampanel, in treating epilepsy, glioma-associated epilepsy and Parkinson's disease is provided. Finally, antisense oligonucleotide therapy as an alternative strategy for the efficient treatment of epilepsy is discussed.

A study of psychogenic non-epileptic seizures in an inpatient video-electroencephalography monitoring service in Tabriz, northwest of Iran.

Background: Psychogenic non-epileptic seizures (PNES) are manifested as paroxysmal alterations in motor, sensory, autonomic, and/or cognitive and behavioral signs and symptoms, without associated ictal epileptiform discharges. A misdiagnosis of PNES as epilepsy results in a prolonged and unnecessary (antiepileptic) drug treatment and social and psychological stigma of epilepsy in these patients. This study aimed to determine the epidemiology, clinical manifestations, and associated factors of PNES in hospitalized patients in the video-electroencephalography (EEG) monitoring (VEM) service of Razi Hospital, Tabriz, Iran. Methods: In this cross-sectional descriptive study, 55 patients with a final diagnosis of PNES were selected from the patients referred to the VEM unit of Razi Hospital for the evaluation of epilepsy. The study was performed from May 2017 to June 2019. Patient information included demographic data and medical history (drug history, comorbidities, trauma, and family history). The clinical manifestations (semiology and duration of attacks) and EEG findings, as recorded by VEM during hospitalization, were collected. Results: 55 patients with PNES were studied with VEM, 27 (49.1%) of which were men, and 28 (50.9%) were women. The mean and standard deviation (SD) of age of the patients was 34.16 ± 12.64 years. No significant differences were observed in the semiology of PNES between men and women. Depression was the most common psychiatric comorbidity. Conclusion: The clinical manifestations of PNES in the present study were similar to those in most previous studies from other countries. The culture and sex of the patients did not seem to be a contributing factor in PNES semiology.

Neurosurgical treatment of nonconvulsive status epilepticus due to focal cortical dysplasia.

We present a rare case of focal cortical dysplasia (FCD) and nonconvulsive status epilepticus (NCSE) treated successfully with early surgical intervention. Our case is a 9-year-old boy whose seizures, characterized by short episodes of loss of consciousness, appeared at the age of 7, and he showed progressive cognitive decline in the following years. NCSE was diagnosed, and his MRI revealed FCD in the left frontal region which was the same side as his EEG abnormality. Following lesionectomy, his NCSE disappeared and cognitive functions improved. Histopathologic analysis of the resected tissue revealed type-IIB FCD. This case illustrates the importance of early surgery to help restore cognitive functions by eliminating the clinical and electrophysiological features of NCSE.