Chronic Central Nervous System Disorders Research Articles

Black Phosphorus Microbubbles Combined with Ultrasound for Treating Parkinson's Disease

AbstractParkinson's disease (PD) is a common chronic central nervous system disorder that reduces quality of life and increases mortality. Currently, the treatment of PD is limited due to the challenge of macromolecular drugs crossing the blood‐brain barrier (BBB). Black phosphorus (BP) has antioxidant and anti‐inflammatory effects and shows potential for neuroprotection. To solve the restriction of the BBB, innovative BP microbubbles (BP@MBs) combined with focused ultrasound (FUS) are constructed to facilitate BBB opening. Additionally, the biocompatibility and safety of BP@MBs with varying dimensions are investigated, including BP quantum dot microbubbles (BPQDs@MBs) and BP nanosheet microbubbles (BPNSs@MBs). The findings indicate that low concentrations of BP have good biosafety and that BPQDs@MBs exhibit better biocompatibility than BPNSs@MBs both in vitro and in vivo at the same concentrations. Moreover, a 6‐hydroxydopamine (6‐OHDA)‐induced PD cell model and an animal model are established to verify the anti‐PD effects of BPQDs@MBs and BPNSs@MBs. The results confirmed that BPQDs@MBs and BPNSs@MBs have antioxidant effects that reduced neuronal apoptosis and improved the motor symptoms of PD in rats. BPQDs@MBs combined with FUS may be a promising option for the clinical treatment of PD.

AMP-activated protein kinase as a mediator of mitochondrial dysfunction of multiple sclerosis in animal models: A systematic review.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) disorder characterized by demyelination, neuronal damage, and oligodendrocyte depletion. Reliable biomarkers are essential for early diagnosis and disease management. Emerging research highlights the role of mitochondrial dysfunction and oxidative stress in CNS disorders, including MS, in which mitochondria are central to the degenerative process. Adenosine monophosphate-activated protein kinase (AMPK) regulates the mitochondrial energy balance and initiates responses in neurodegenerative conditions. This systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aimed to comprehensively assess the literature on AMPK pathways, mitochondrial dysfunction, and in vivo studies using MS animal models. The search strategy involved the use of AMPK syntaxes, MS syntaxes, and animal model syntaxes. The PubMed, Scopus, Web of Science, and Google Scholar databases were systematically searched onAugust 26, 2023 without publication year restrictions. The review identified and analyzed relevant papers to provide a comprehensive overview of the current state of related research. Eight studies utilizing various interventions and methodological approaches were included. Risk of bias assessment revealed some areas of low risk but lacked explicit reporting in others. These studies collectively revealed a complex relationship between AMPK, mitochondrial dysfunction, and MS pathogenesis, with both cuprizone and experimental autoimmune encephalomyelitis models demonstrating associations between AMPK and mitochondrial disorders, including oxidative stress and impaired expression of mitochondrial genes. These studies illuminate the multifaceted role of AMPK in MS animal models, involving energy metabolism, inflammatory processes, oxidative stress, and gene regulation leading to mitochondrial dysfunction. However, unanswered questions about its mechanisms and clinical applications underscore the need for further research to fully harness its potential in addressing MS-related mitochondrial dysfunction.

Metabolic Control of Microglia.

Microglia, immune sentinels of the central nervous system (CNS), play a critical role in maintaining its health and integrity. This chapter delves into the concept of immunometabolism, exploring how microglial metabolism shapes their diverse immunefunctions. It examines the impact of cell metabolism on microglia during various CNS states, including homeostasis, development, aging, and inflammation. Particularly in CNS inflammation, the chapter discusses how metabolic rewiring in microglia can initiate, resolve, or perpetuate inflammatory responses. The potential of targeting microglial metabolism as a therapeutic strategy for chronic CNS disorders with prominent innateimmune cellactivation is also explored.

Особенности биоэлектрической активности ретросплениальной коры головного мозга

Human brain is one of the most difficult organs to study. The possibility of developing the technologies that have sufficient scientific accuracy and economic accessibility and never violate the moral and ethical standards of human society is of great interest. The study was aimed to study the possibility of assessing the retrosplenial cortex (RSC) structures’ activity based on the EEG analysis of brain activity in the alpha frequency range in 36 healthy volunteers with an average age of 29.1 years, no acute central nervous system disorders or exacerbation of chronic central nervous system disorders, severe traumatic brain injuries, mental disorders or epilepsy. Significant source localizations were obtained by solving the EEG inverse problem that could be used for identification of the cerebral retrosplenial cortex structures’ bioelectric activity. The use of such technology will allow us to expand the scope of the research focused on assessing the brain functional activity in both research and clinical centers, thereby paving the way for understanding the features of the brain structures’ activity in physiologically normal conditions and in individuals with mental disorders caused by various functional alterations in the brain.

Magnetoencephalography-based approaches to epilepsy classification.

Epilepsy is a chronic central nervous system disorder characterized by recurrent seizures. Not only does epilepsy severely affect the daily life of the patient, but the risk of premature death in patients with epilepsy is three times higher than that of the normal population. Magnetoencephalography (MEG) is a non-invasive, high temporal and spatial resolution electrophysiological data that provides a valid basis for epilepsy diagnosis, and used in clinical practice to locate epileptic foci in patients with epilepsy. It has been shown that MEG helps to identify MRI-negative epilepsy, contributes to clinical decision-making in recurrent seizures after previous epilepsy surgery, that interictal MEG can provide additional localization information than scalp EEG, and complete excision of the stimulation area defined by the MEG has prognostic significance for postoperative seizure control. However, due to the complexity of the MEG signal, it is often difficult to identify subtle but critical changes in MEG through visual inspection, opening up an important area of research for biomedical engineers to investigate and implement intelligent algorithms for epilepsy recognition. At the same time, the use of manual markers requires significant time and labor costs, necessitating the development and use of computer-aided diagnosis (CAD) systems that use classifiers to automatically identify abnormal activity. In this review, we discuss in detail the results of applying various different feature extraction methods on MEG signals with different classifiers for epilepsy detection, subtype determination, and laterality classification. Finally, we also briefly look at the prospects of using MEG for epilepsy-assisted localization (spike detection, high-frequency oscillation detection) due to the unique advantages of MEG for functional area localization in epilepsy, and discuss the limitation of current research status and suggestions for future research. Overall, it is hoped that our review will facilitate the reader to quickly gain a general understanding of the problem of MEG-based epilepsy classification and provide ideas and directions for subsequent research.

Neuroprotective effects of hesperetin on H2O2-induced damage in neuroblastoma SH-SY5Y cells.

Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H2O2)-treated SH-SY5Y cells. SH-SY5Y cells were treated with H2O2 (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H2O2-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H2O2-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H2O2-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H2O2-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

Surgical outcome of male patients with chronic central nervous system disorders and voiding dysfunction due to bladder outlet obstruction.

Voiding dysfunction is common in patients with chronic central nervous system (CNS) diseases and has great impact on quality of life. Patients with chronic CNS disorders might have concomitant detrusor overactivity, detrusor underactivity, and voiding dysfunction. Although bladder outlet surgeries could relieve bladder outlet obstruction (BOO), patients might have persistent or exacerbated storage symptoms. This study investigated surgical outcome of patients with chronic CNS disorders after bladder outlet surgery. A total of 63 male patients with cerebrovascular accident (CVA, n = 44), Parkinson's disease (PD, n = 11), and early-stage dementia (n = 8), had received bladder outlet surgery after videourodynamic proven BOO refractory to medical treatment. The preoperative and postoperative lower urinary tract symptoms (LUTS) and uroflowmetry parameters were assessed. If the storage symptom subscore decreased or increased by 1, the outcome was considered improved or exacerbated after treatment. When patients had improvement in maximum flow rate (Qmax) and voiding efficiency (VE) and decreased voiding symptom subscore, they were considered having improvement of voiding dysfunction. The mean age was 71.1 ± 9.8years and mean duration from diagnosis of BOO to surgical intervention was 15.1 ± 25.0months. Overall, there was significant improvement in voiding LUTS and urinary retention after surgery. The post-void residual volume (PVR), corrected Qmax (cQmax), and VE significantly improved after surgery. In subgroup analysis, although voiding symptoms improved in CVA patients, urgency and exacerbated urgency incontinence persisted after surgery. In PD patients, there was improvement in voiding condition such as PVR, cQmax and VE, but the storage symptoms did not change after surgery. Patients with dementia had no improvement both in storage and voiding symptoms. Bladder outlet surgeries are effective to relieve voiding dysfunction in patients with CVA and PD, but have little effect on storage LUTS in patients with chronic brain lesions.

Remote Assessments of Hand Function in Neurological Disorders: Systematic Review.

BackgroundLoss of fine motor skills is observed in many neurological diseases, and remote monitoring assessments can aid in early diagnosis and intervention. Hand function can be regularly assessed to monitor loss of fine motor skills in people with central nervous system disorders; however, there are challenges to in-clinic assessments. Remotely assessing hand function could facilitate monitoring and supporting of early diagnosis and intervention when warranted.ObjectiveRemote assessments can facilitate the tracking of limitations, aiding in early diagnosis and intervention. This study aims to systematically review existing evidence regarding the remote assessment of hand function in populations with chronic neurological dysfunction.MethodsPubMed and MEDLINE, CINAHL, Web of Science, and Embase were searched for studies that reported remote assessment of hand function (ie, outside of traditional in-person clinical settings) in adults with chronic central nervous system disorders. We excluded studies that included participants with orthopedic upper limb dysfunction or used tools for intervention and treatment. We extracted data on the evaluated hand function domains, validity and reliability, feasibility, and stage of development.ResultsIn total, 74 studies met the inclusion criteria for Parkinson disease (n=57, 77% studies), stroke (n=9, 12%), multiple sclerosis (n=6, 8%), spinal cord injury (n=1, 1%), and amyotrophic lateral sclerosis (n=1, 1%). Three assessment modalities were identified: external device (eg, wrist-worn accelerometer), smartphone or tablet, and telerehabilitation. The feasibility and overall participant acceptability were high. The most common hand function domains assessed included finger tapping speed (fine motor control and rigidity), hand tremor (pharmacological and rehabilitation efficacy), and finger dexterity (manipulation of small objects required for daily tasks) and handwriting (coordination). Although validity and reliability data were heterogeneous across studies, statistically significant correlations with traditional in-clinic metrics were most commonly reported for telerehabilitation and smartphone or tablet apps. The most readily implementable assessments were smartphone or tablet-based.ConclusionsThe findings show that remote assessment of hand function is feasible in neurological disorders. Although varied, the assessments allow clinicians to objectively record performance in multiple hand function domains, improving the reliability of traditional in-clinic assessments. Remote assessments, particularly via telerehabilitation and smartphone- or tablet-based apps that align with in-clinic metrics, facilitate clinic to home transitions, have few barriers to implementation, and prompt remote identification and treatment of hand function impairments.

The Effect of Valproate Sodium on the Electrical Activity of Helix aspersa F1 Neurons in a Pentylenetetrazole-Induced Epileptic Model Using an Intracellular Recording System

Background: Epilepsy is a chronic central nervous system disorder with a high prevalence in modern society. Despite using common anticonvulsant drugs, its control is not adequately achieved. Animal models for seizures play the leading role in advancing our understanding of the cellular mechanisms of epilepsy. The present study was an attempt to elucidate the electrophysiological mechanism of the effect of sodium valproate on the cellular model of epilepsy. Understanding the cellular mechanisms of this drug may help clarify the pharmacological screening of other drugs. Methods: The intracellular recording was made from F1 cells of garden Helix aspersa in the presence of Ringer solution. Following the extracellular application of valproate sodium at a concentration of 10 mM after and before the use of (25mM) epileptogenic agent (pentylenetetrazol (PTZ)), we evaluated its effect on paroxysmal depolarization shift (PDS) and electrophysiological characteristics. Results: These results showed that valproate sodium could reduce neuronal excitability. It could significantly hyperpolarize rest action potential by decreasing the frequency of firing rate and increasing the amplitude of afterhyperpolarization (AHP) and can prevent depolarization of rest action potential by PTZ. Conclusions: The results suggested that valproate sodium could reduce the PTZ-induced hyperexcitation by hyperpolarization of resting membrane potential (RMP), a reduction in AHP amplitude, and firing the frequency.

Preparation, physicochemical and biopharmaceutical characterization of oxcarbazepine-loaded nanostructured lipid carriers as potential antiepileptic devices

Epilepsy is the second most common chronic central nervous system disorder. Oxcarbazepine (OXC) is an antiepileptic drug with low solubility in aqueous media but is used for the treatment of both focal and generalized seizures. Studies of OXC encapsulation in nanostructured lipid carriers (NLCs) composed of cetyl palmitate and oleic acid coated with polyvinyl alcohol (PVA) or chitosan (Ch) to obtain nanoparticles with negative and positive surface charge, respectively, are reported. All NLCs displayed 97%–98% OXC encapsulation efficiency, 14.5%–14.6% drug loading, 121.8–212.3 nm size range, and polydispersity indexes between 0.248 and 0.282 nm, depending on their composition. The homogeneity of the NLCs was confirmed by electron microscopy. The OXC release from the NLCs was analyzed by Higuchi, Baker-Londsdale, and Korsmeyer-Peppas structured models. The Korsmeyer-Peppas model provides the best data fit (R2 > 0.98), and n > 0.58, suggesting a mechanism driven by non-Fickian molecular release. In vitro permeability studies using MDCK-MDR1 cells revealed enhanced permeability of the encapsulated drug compared with free OXC. Surface plasmon resonance tested in the presence of BSA, IgG, and IgM, commonly found in human plasma, revealed no interaction with naked and PVA-coated NLCs. These promising results allow considering further in vivo studies for efficient delivery of OXC.

Intranasal delivery of topiramate nanoemulsion: Pharmacodynamic, pharmacokinetic and brain uptake studies

Epilepsy is the noncommunicable and chronic central nervous system disorder characterized by frequent, unprovoked seizures, or electrical disturbances in the brain. Topiramate is used as an antiepileptic drug for the treatment of partial onset seizures, generalized seizures and Lennox-Gastaut Syndrome. Topiramate, a BCS class II drug, has a relatively low bioavailability. It is also a substrate of P-glycoprotein and Blood Brain Barrier restricts its entry into the brain. This investigation was aimed to prepare O/W nanoemulsion delivery system of topiramate to improve its brain bioavailability. Topiramate loaded nanoemulsion was prepared by phase titration method. It was consisting of 2% w/w Capmul MCM C8, 32% w/w Tween 20:Carbitol (2:1) and 66% w/w water. It was characterized for globule size, viscosity, polydispersibility index, zeta potential, pH, conductivity values, transmittance and TEM. Pharmacodynamic, pharmacokinetic and brain drug uptake study was carried out using wistar albino rats post intranasal and oral administration. Topiramate loaded nanoemulsion was having a globule size of 4.73±0.52nm. It was stable for six months. Brain uptake of topiramate post intranasal administration of topiramate loaded nanoemulsion was significantly (P<1.86×10-8) higher when it was compared with oral administration of topiramate loaded nanoemulsion. This study indicates that intranasal administration of topiramate containing nanoemulsion could be an encouraging approach for the treatment of epilepsy to minimize the dose of topiramate in direction to avoid dose related adverse events.

Antiepileptic potential of Bacopa monnieri in the rat brain during PTZ-induced epilepsy with reference to cholinergic system and ATPases

Epilepsy is a chronic central nervous system disorder that occurs not only with the imbalance of glutamatergic neurons and inhibitory gamma-aminobutyric acid (γ-GABA) neurons, but also with abnormal Central cholinergic neuronal regulation. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistance and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for the treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compound with particular reference to Cholinergic system and ATPases in different brain regions of rat to explore the possible antiepileptic effect of different extracts of BM in comparison with Diazepam (DZ) (Reference control). The activity levels of Acetyl cholinesterase (AChE) and ATPases were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. In addition Acetylcholine (ACh), levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade that occurs during epileptogenesis.

In Vitro and Ex Vivo Model Systems to Measure ABC Transporter Activity at the Blood-Brain Barrier.

With the aging population the occurrence of central nervous system diseases such as cancer, mental disorders and neurodegenerative diseases, is expected to increase and hence, the demand for effective drugs. However, the passage of drugs across the blood-brain barrier represents a major challenge in accomplishing efficient brain delivery of therapeutic agents. This highly efficient barrier is composed of a monolayer of capillary endothelial cells supported by pericytes and astrocytic end-feet, that together effectively shield the brain from the blood. The brain microvascular endothelial cells form a physical and metabolic barrier where paracellular and transcellular transport of molecules in and out of the brain is closely regulated, allowing nutrients to pass but preventing the entry of harmful neurotoxic substances, including drugs. For this purpose brain endothelial cells express efficient efflux pumps, such as ATP binding cassette (ABC) transporters, which limit the delivery of drugs into the brain. To treat the above-mentioned chronic central nervous system disorders, it is crucial to design compounds that can pass the blood-brain barrier and thus the ABC transporters. In order to achieve this, representative models of the blood-brain barrier with predictive validity are necessary. This review discusses the current in vitro and ex vivo model systems that are used to measure ABC transporter activity in order to study potential in vivo efficacy of blood-brain barrier-drug passage.

Second‐Generation Non‐Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis

AbstractPalmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N‐acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti‐inflammatory therapy, the lipid‐like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole–piperazine derivatives that inhibit NAAA in a potent and selective manner by a non‐covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non‐covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders.

Second‐Generation Non‐Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders.

The dynamic blood-brain barrier.

With the endothelium as its central unit, the blood-brain barrier (BBB) is a complex multicellular structure separating the central nervous system (CNS) from the systemic circulation. Disruption of the BBB has now been implicated in a multitude of acute and chronic CNS disorders indicating the potentially devastating effects of BBB breakdown on brain function. However, the healthy BBB is not an impermeable wall, but rather a communication 'centre', responding to and passing signals between the CNS and blood. New studies are identifying BBB-specific transport pathways that tightly regulate the entry and exit of molecules to and from the brain. They are revealing a highly plastic barrier in which dynamic changes in BBB components like paracellular tight junction complexes can contribute to BBB maintenance. Here, we provide a succinct overview of the current state-of-play in BBB research and summarize novel findings into BBB regulation in homeostatic regulation of the brain.

Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes.

Psychological Management of Craving

Drug addiction constitutes a chronic central nervous system disorder and one of the most serious public health problems globally, not only because of their high prevalence and impact on the personal, family, occupational and social spheres, but also because of their economic and medical consequences. Most prominent features of addictive behavior are craving which can be described as the psychic pain of addiction. It is an intractable obstacle confronted by addicts attempting to achieve abstinence. Craving is the key in evolving drug-taking behavior into compulsive drug-taking behavior. Cravings for food are similar to substance cravings in their maladaptive potential to cause eating disorders. Direct relationship between craving and relapse, though not easily established, appears to occur through intermediate factors. Incorporating craving measurements in routine clinical practice can increase the patient’s capability to know and monitor his internal states that are related to substance intake and this can be used in recommending appropriate treatment. Craving seems to be a non-unitary phenomenon, and different kinds of craving with different mechanisms have been proposed, so it is conceivable that different drugs (including proposed immunotherapy) can be more or less effective on different kinds of craving. Hence there is great need for psychological management as augmented and maintenance strategy.

Compensation for occupational neurological and mental disorders.

Standards for the recognition of occupational diseases (ODs) in Korea were established in 1954 and have been amended several times. In 2013, there was a significant change in these standards. On the basis of scientific evidence and causality, the International Labour Organization list, European Commission schedule, and compensated cases in Korea were reviewed to revise the previous standards for the recognition of ODs in Korea. A disease-based approach using the International Classification of Diseases (10th version) was added on the previous standards, which were agent-specific approaches. The amended compensable occupational neurological disorders and occupational mental disorders (OMDs) in Korea are acute and chronic central nervous system (CNS) disorders, toxic neuropathy, peripheral neuropathy, manganese-related disorders, and post-traumatic stress disorder. Several agents including trichloroethylene (TCE), benzene, vinyl chloride, organotin, methyl bromide, and carbon monoxide (CO) were newly included as acute CNS disorders. TCE, lead, and mercury were newly included as chronic CNS disorders. Mercury, TCE, methyl n-butyl ketone, acrylamide, and arsenic were newly included in peripheral neuropathy. Post-traumatic stress disorders were newly included as the first OMD. This amendment makes the standard more comprehensive and practical. However, this amendment does not perfectly reflect the recent scientific progress and social concerns. Ongoing effort, research, and expert consensus are needed to improve the standard.

Herbal and synthetic approaches for the treatment of epilepsy

The term epilepsy is collectively designated for a group of chronic central nervous system disorders characterized by spontaneous occurrence of seizures generally associated with the loss of consciousness and body movements (convulsions). Anticonvulsant drugs are used to control the convulsions by inhibiting the discharge and then producing hypnosis. Various synthetic drugs, viz. phenytoin (PHT), diazepam, valproate (VPA), leviteracetam, etc., are used for the treatment. These agents have a new spectrum of efficacy and novel adverse effects. They also represent an enormous escalation of costs. At present, herbal therapies are tried by patients in developing as well as developed countries for control of seizures or adverse effects from antiepileptic drugs, or for general health maintenance. There are number of synthetic drugs available for treatment of epilepsy in modern therapy, but the major disadvantage being faced is their chronic side effects. Treatment of epilepsy with herbal drugs as adjuvant seems to be more beneficial and is gaining more popularity due to their fewer side effects.