Showing papers in "Expert Review of Neurotherapeutics in 2021"
TL;DR: The use of istradefylline in the treatment of Parkinson's disease is limited to the management of motor fluctuations as supported by the results of randomized clinical trials and evaluation by Japanese and USA regulatory authorities as mentioned in this paper.
Abstract: Introduction It is now accepted that Parkinson's disease (PD) is not simply due to dopaminergic dysfunction, and there is interest in developing non-dopaminergic approaches to disease management. Adenosine A2A receptor antagonists represent a new way forward in the symptomatic treatment of PD.Areas covered In this narrative review, we summarize the literature supporting the utility of adenosine A2A antagonists in PD with a specific focus on istradefylline, the most studied and only adenosine A2A antagonist currently in clinical use.Expert opinion: At this time, the use of istradefylline in the treatment of PD is limited to the management of motor fluctuations as supported by the results of randomized clinical trials and evaluation by Japanese and USA regulatory authorities. The relatively complicated clinical development of istradefylline was based on classically designed studies conducted in PD patients with motor fluctuations on an optimized regimen of levodopa plus adjunctive dopaminergic medications. In animal models, there is consensus that a more robust effect of istradefylline in improving motor function is produced when combined with low or threshold doses of levodopa rather than with high doses that produce maximal dopaminergic improvement. Exploration of istradefylline as a 'levodopa sparing' strategy in earlier PD would seem warranted.
43 citations
TL;DR: Metformin, through activation of AMPK and autophagy, can enhance neuronal bioenergetics, promote nerve repair and reduce toxic protein aggregates in neurological diseases.
Abstract: Introduction: Metformin is currently first line therapy for type 2 diabetes (T2D). The mechanism of action of metformin involves activation of AMP-activated protein kinase (AMPK) to enhance mitocho...
34 citations
TL;DR: The Ganaxolone (GNX) is a synthetic analog of the endogenous neurosteroid allopregnanolone and a member of a novel class of neuroactive steroids called epalons as discussed by the authors.
Abstract: Introduction: Nonsulfated neurosteroids can provide phasic and tonic inhibition through activation of synaptic and extra-synaptic γ-aminobutyric acid (GABA)A receptors, exhibiting a greater potency for the latter. These actions occur by interacting with modulatory sites that are distinct from those bound by benzodiazepines and barbiturates. Ganaxolone (GNX) is a synthetic analog of the endogenous neurosteroid allopregnanolone and a member of a novel class of neuroactive steroids called epalons.Areas covered: The authors review the pharmacology of GNX, summarize the main clinical evidence about its antiseizure efficacy and tolerability, and suggest implications for clinical practice and future research.Expert opinion: The clinical development of GNX is mainly oriented to target unmet needs and focused on status epilepticus and rare genetic epilepsies that have few or no treatment options.The availability of oral and intravenous formulations allows reaching adult and pediatric patients in acute and chronic care settings. Further evidence will complement the understanding of the potentialities of GNX and possibly lead to indications for use in clinical practice.
26 citations
TL;DR: This article evaluated the safety and efficacy of Valbenazine in the treatment of involuntary tics associated with Tourette syndrome (TS) in adult and pediatric subjects, and found that the treatment was generally well-tolerated in the studies, and treatment-emergent adverse events were consistent with valbenazine studies in tardive dyskinesia (TD).
Abstract: Introduction: Significant need exists for effective, well-tolerated pharmacologic treatments for Tourette syndrome (TS). Medications that inhibit vesicular monoamine transporters (i.e. VMAT2 inhibitors) downregulate presynaptic packaging and release of dopamine into the neuronal synapse and are effective in treating hyperkinetic movement disorders such as Huntington's chorea and tardive dyskinesia (TD); thus, they may be useful in treating TS.Areas covered: This review describes the clinical program evaluating the safety and efficacy of valbenazine in the treatment of involuntary tics associated with TS in adult and pediatric subjects. While there was a trend in the 6 completed trials toward greater improvement in valbenazine-treated versus placebo subjects on the primary efficacy endpoint (Yale Global Tic Severity Scale Total Tic Score), this difference did not reach statistical significance. Valbenazine was generally well-tolerated in the studies, and treatment-emergent adverse events were consistent with valbenazine studies in TD.Expert opinion: Due to the failure to meet the primary endpoint in these trials, further investigation of valbenazine for TS is unlikely. Given the need for safe and effective TS therapies and the key role of VMAT2 in modulating dopaminergic activity, it is reasonable for future studies to investigate other VMAT2 inhibitors as potential treatments for TS.
22 citations
TL;DR: In this article, the authors review the current evidence on nutrition-mood interaction and nutrition-based treatments for the two main mood disorders, i.e., major depressive disorder and bipolar disorder.
Abstract: Introduction: 'Nutritional Psychiatry' is an emerging area of research that has great potential as an adjunctive tool for the prevention and treatment of diverse neuropsychiatric disorders. Several nutrition-related aspects, such as obesity, dietary patterns, gut microbiome composition and gut permeability, bioactive food compounds, and nutrients can influence pathways implicated in the pathophysiology of mood disorders.Areas covered: Here, the authors review the current evidence on nutrition-mood interaction and nutrition-based treatments for the two main mood disorders, i.e., major depressive disorder and bipolar disorder.Expert opinion: Consistent evidence from observational studies has pointed out the association between a 'healthy' diet, generally characterized by a higher intake of fruits, vegetables, legumes, nuts, whole grains, and good quality sources of protein (i.e. fish and/or seafood), and decreased risk of mood disorders and the parallel association between a 'Western' diet pattern and increased risk. However, only a few clinical trials have evaluated the effect of nutritional interventions on the treatment of these conditions. The bidirectional interaction between the brain and the gut, named 'brain-gut-microbiome axis' or 'gut-brain axis', plays a key role in the link between nutrition and mood disorders. Therefore, nutrition-based strategies for gut microbiota modulation are promising fields in mood disorders.
20 citations
TL;DR: In this article, the authors reported that diabetes is an increasingly prevalent disorder affecting nearly 1-in-5 adults, of which half will experience diabetic peripheral neuropathy (DPN) and a quarter will suffer from diabetic peripheral...
Abstract: Diabetes is an increasingly prevalent disorder affecting nearly 1-in-5 adults, of which half will experience diabetic peripheral neuropathy (DPN) and a quarter will suffer from diabetic peripheral ...
20 citations
TL;DR: This review will critically review the pharmacokinetic properties of CBD, the interactions with antiseizur and non-antiseizure medications, and the main tolerability and safety issues to provide guidance for its use in everyday practice.
Abstract: Pharmaceutically purified oral cannabidiol (CBD) has been recently approved by the US Food and Drug Administration and European Medicines Agency as treatment of seizures associated with Dravet synd...
18 citations
TL;DR: In this paper, the authors discuss the current SARS-Cov-2 pandemic and the increased risk of post-intensive care syndrome (PICS) in these post-ICU patients and their families.
Abstract: INTRODUCTION: Post-intensive care syndrome (PICS) has only recently been recognized as a new clinical entity in patients surviving their intensive care unit (ICU) stay due to critical illness. With increasing survival rates of ICU patients worldwide, there is a rising interest regarding post-ICU recovery. AREAS COVERED: First, based on the current literature a definition is provided of PICS, including the domains of impairments that comprise PICS along with the etiology and risk factors. Second, preventive measures and possible treatment strategies integrated in the follow-up care are described. Third, the authors will discuss the current SARS-Cov-2 pandemic and the increased risk of PICS in these post-ICU patients and their families. EXPERT OPINION: PICS is a relatively new entity, which not only encompasses various physical, cognitive, and psychological impairments but also impacts global health due to long-lasting detrimental socioeconomic burdens. Importantly, PICS also relates to caregivers of post-ICU patients. Strategies to reduce this burden will not only be needed within the ICU setting but will also have to take place in an interdisciplinary, multifaceted approach in primary care settings. Additionally, the SARS-Cov-2 pandemic has a high burden on post-ICU patients and their relatives.
16 citations
TL;DR: This paper presents a comprehensive review of the recent developments in the field of robot-assisted ankle rehabilitation in the context of the evaluation of robotic hardware with healthy subjects as well as motor function outcomes with neurologically impaired subjects.
Abstract: Introduction: Robot-assisted neuro-rehabilitation is gaining acceptability among the physical therapy community. The ankle is one of the most complicated anatomical joints in the human body and neu...
16 citations
TL;DR: The role of environmental factors in the pathogenesis and progression of multiple sclerosis (MS), either acting alone or by interacting with other environmental or genetic factors, is discussed in this paper.
Abstract: Introduction: Environmental factors play a significant role in the pathogenesis and progression of multiple sclerosis (MS), either acting alone or by interacting with other environmental or genetic factors. This cumulative exposure to external risk factors is highly complex and highly variable between individuals. Areas covered: We narratively review the current evidence on the role of environment-specific risk factors in MS onset and progression, as well as the effect of gene-environment interactions and the timing of exposure We have reviewed the latest literature, by Ovid Medline, retrieving the most recently published systematic reviews and/or meta-analyses and more recent studies not previously included in meta-analyses or systematic reviews. Expert opinion: There is some good evidence supporting the impact of some environmental risk factors in increasing the risk of developing MS. Tobacco smoking, low vitamin D levels and/or low sun exposure, Epstein Barr Virus (EBV) seropositivity and a history of infectious mononucleosis may increase the risk of developing MS. Additionally, there is some evidence that gene-smoking, gene-EBV, and smoking-EBV interactions additively affect the risk of MS onset. However, the evidence for a role of other environmental factors in MS progression is limited. Finally, there is some evidence that tobacco smoking, insufficient vitamin D levels and/or sun exposure have impacts on MS phenotypes and various markers of disease activity including relapse, disability progression and MRI findings. Clearly the effect of environmental factors on MS disease course is an area that requires significantly more research.
16 citations
TL;DR: A review of the advances in the diagnosis and treatment of focal cortical dysplasias (FCDs) with a special focus on the novel therapeutic options prompted by a better understanding of their pathophysiology is presented in this article.
Abstract: Introduction Focal cortical dysplasias (FCDs) represent the most common etiology in pediatric drug-resistant focal epilepsies undergoing surgical treatment The localization, extent and histopathological features of FCDs are considerably variable Somatic mosaic mutations of genes that encode proteins in the PI3K-AKTmTOR pathway, which also includes the tuberous sclerosis associated genes TSC1 and TSC2, have been implicated in FCD type II in a substantial subset of patients Surgery is the principal therapeutic option for FCD-related epilepsy Advanced neurophysiological and neuroimaging techniques have improved surgical outcome and reduced the risk of postsurgical deficits Pharmacological MTOR inhibitors are being tested in clinical trials and might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease, used alone or in combination with surgery Areas covered This review will critically analyze the advances in the diagnosis and treatment of FCDs, with a special focus on the novel therapeutic options prompted by a better understanding of their pathophysiology Expert opinion Focal cortical dysplasia is a main cause of drug-resistant epilepsy, especially in children Novel, personalized approaches are needed to more effectively treat FCD-related epilepsy and its cognitive consequences
TL;DR: In this paper, the authors proposed wearable sensor technology for motor complication management in Parkinson's disease patients, which can provide sustained, near-to-physiological inputs to dysfunctional basal ganglia-cortical circuits over time.
Abstract: Introduction Motor complication management is one of the main unmet needs in Parkinson's disease patients. Areas covered Among the most promising emerging approaches for handling motor complications in Parkinson's disease, adaptive deep brain stimulation strategies operating in closed-loop have emerged as pivotal to deliver sustained, near-to-physiological inputs to dysfunctional basal ganglia-cortical circuits over time. Existing sensing systems that can provide feedback signals to close the loop include biochemical-, neurophysiological- or wearable-sensors. Biochemical sensing allows to directly monitor the pharmacokinetic and pharmacodynamic of antiparkinsonian drugs and metabolites. Neurophysiological sensing relies on neurotechnologies to sense cortical or subcortical brain activity and extract real time correlates of symptom intensity or symptom control during DBS. A more direct representation of the symptom state, particularly the phenomenological differentiation and quantification of motor symptoms, can be realized via wearable sensor technology. Expert opinion Biochemical, neurophysiologic, and wearable-based biomarkers are promising technological tools that either individually or in combination could guide adaptive therapy for Parkinson's disease motor symptoms in the future.
University of Cambridge1, University of Padua2, Ludwig Maximilian University of Munich3, Paracelsus Private Medical University of Salzburg4, Chulalongkorn University5, Royal Society6, University of São Paulo7, University of Malaya8, North Bristol NHS Trust9, Northumbria Healthcare NHS Foundation Trust10, Instituto de Medicina Molecular11, King's College London12, University of Alberta13
TL;DR: In this article, the authors outline some motor and non-motor symptoms relevant to palliative care and propose a pragmatic and rapidly deployable, consensus-based approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.
Abstract: Introduction: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities.Areas covered: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly - as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.Expert opinion: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms - both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term.
TL;DR: Aphasia diagnosis has largely evolved beyond the traditional approach of classifying patients into specific syndromes and instead focuses on individualized patient profiles and there is a great need for more large scale randomized, double-blind, placebo-controlled clinical trials of behavioral treatments, noninvasive brain stimulation, and medications to boost aphasia recovery.
Abstract: Introduction: Aphasia is a debilitating language disorder and even mild forms of aphasia can negatively affect functional outcomes, mood, quality of life, social participation, and the ability to return to work. Language deficits after post-stroke aphasia are heterogeneous. Areas covered: The first part of this manuscript reviews the traditional syndrome-based classification approach as well as recent advances in aphasia classification that incorporate automatic speech recognition for aphasia classification. The second part of this manuscript reviews the behavioral approaches to aphasia treatment and recent advances such as noninvasive brain stimulation techniques and pharmacotherapy options to augment the effectiveness of behavioral therapy. Expert opinion: Aphasia diagnosis has largely evolved beyond the traditional approach of classifying patients into specific syndromes and instead focuses on individualized patient profiles. In the future, there is a great need for more large scale randomized, double-blind, placebo-controlled clinical trials of behavioral treatments, noninvasive brain stimulation, and medications to boost aphasia recovery.
TL;DR: Thrombolysis, antiplatelet and anticoagulation therapy, their efficacy has been well-established and future research efforts should be directed toward adjusting its use according to patient-specific factors, starting with factors with the most clinical relevance and prevalence.
Abstract: Amongst the 25.7 million survivors and 6.5 million deaths from stroke between 1990 and 2013, ischemic strokes accounted for approximately 70% and 50% of the cases, respectively. With patients still...
TL;DR: In this paper, a review of the differences in men and women with schizophrenia is presented, focusing on the ones that carry important implications for clinical care: effective antipsychotic doses, medication side effects, symptom fluctuation due to hormonal levels, comorbidities, and women's requirements for prenatal, obstetric, postpartum, and parenting support.
Abstract: Introduction: Most medical diagnoses present somewhat differently in men and women, more so at specific periods of life. Treatment effects may also differ. This is true for schizophrenia, where premorbid effects are experienced earlier in life in boys than in girls, and where symptoms and outcomes differ.Areas covered: This review does not cover all the differences that have been reported between men and women but, instead, focuses on the ones that carry important implications for clinical care: effective antipsychotic doses, medication side effects, symptom fluctuation due to hormonal levels, comorbidities, and women's requirements for prenatal, obstetric, postpartum, and parenting support.Expert opinion: Of consequence to schizophrenia, sex-biased genes, epigenetic modifications, and sex steroids all impact the structure and function of the brain. Furthermore, life experiences and social roles exert major sex-specific influences. The co-morbidities that accompany schizophrenia also affect men and women to different degrees. This review offers several examples of sex-specific intervention and concludes that gold standard treatment must look beyond symptoms and address all the physiologic, psychologic, and social role needs of men and women suffering from this psychiatric disorder.
TL;DR: Iiopathic intracranial hypertension is a condition characterized by raised intra-brachial pressure, papilledema, and normal neuroimaging (aside from radiological signs of raised intraclanial pressure) as discussed by the authors.
Abstract: Introduction: Idiopathic intracranial hypertension is a condition characterized by raised intracranial pressure, papilledema, and normal neuroimaging (aside from radiological signs of raised intrac...
TL;DR: In this paper, the most popular and effective nutraceuticals with proposed brief mechanisms entailing antioxidant, anti-inflammatory, autophagy regulation, mitochondrial homeostasis, and more.
Abstract: Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanying memory deficits. The available pharmaceutical care has some limitations mostly entailing side effects, shelf-life, and patient's compliance. The momentous implications of nutraceuticals in AD have attracted scientists. Several preclinical studies for the investigation of nutraceuticals have been conducted.Areas covered: This review focuses on the potential use of a nutraceuticals-based therapeutic approach to treat and prevent AD. Increasing knowledge of AD pathogenesis has led to the discovery of new therapeutic targets including pathophysiological mechanisms and various cascades. Hence, the present contribution will attend to the most popular and effective nutraceuticals with proposed brief mechanisms entailing antioxidant, anti-inflammatory, autophagy regulation, mitochondrial homeostasis, and more. Therefore, even though the effectiveness of nutraceuticals cannot be dismissed, it is essential to do further high-quality randomized clinical trials.Expert opinion: According to the potential of nutraceuticals to combat AD as multi-target directed drugs, there is critical importance to assess them as feasible lead compounds for drug discovery and development. To the best of the authors' knowledge, modification of blood-brain barrier permeability, bioavailability, and features of randomized clinical trials should be considered in prospective studies.
TL;DR: In this review, the authors focused on certain hot-topic issues in the field: the respective contribution of the cerebellum and striatum to the generation of paroxysmal dyskinesia, the importance of striatal cAMP turnover in the pathogenesis of par oxysmal Dyskinesian disorders, and the treatable causes of parxysmal movement disorders.
Abstract: Paroxysmal movement disorders mostly comprise paroxysmal dyskinesia and episodic ataxia, and can be the consequence of a genetic disorder or symptomatic of an acquired disease. In this review, the ...
TL;DR: In this article, the gold-standard Parkinson's disease treatment, Levodopa, remains the gold standard Parkinson's treatment, but the inevitable development of motor complications has led to intense activity in pursuit of its optimal delivery.
Abstract: Levodopa remains the gold-standard Parkinson’s disease (PD) treatment, but the inevitable development of motor complications has led to intense activity in pursuit of its optimal delivery.Periphera...
TL;DR: A systematic review and meta-analysis were carried out according to PRISMA guidelines as mentioned in this paper, where computer-based interventions, cognitive-behavioral therapy and assisted-animal therapy were evaluated.
Abstract: INTRODUCTION . Children with Autism Spectrum Disorder (ASD) experience difficulties in Executive Functions (EF) performances. However, efficacy of EF intervention needs to be further investigated. OBJECTIVE to evaluate the efficacy of different EF interventions in children and adolescents with ASD. METHODS A systematic review and meta-analysis were carried out according to PRISMA guidelines. Relevant databases including Pubmed, Psychinfo, Scopus and Web of Science were searched up to November 2019. Papers included in the study have the following characteristics: randomized controlled trial or quasi-experimental design and be published in English or Spanish. RESULTS After the elimination of duplicates, 949 were screened. Among these six were included in the systematic review. The main approaches for EF in ASD were computer-based interventions, cognitive-behavioral therapy and assisted-animal therapy. Statistically significant results (p=0.003) were found in using exergames. CONCLUSION Different approaches can be used for improving EF intervention, with positive effects on working memory, behavior, and flexibility.
TL;DR: Post-traumatic headache (PTH), a common type of headache secondary to traumatic brain injury (TBI) or whiplash, carries a relevant burden on patients as discussed by the authors.
Abstract: Post-traumatic headache (PTH), a common type of headache secondary to traumatic brain injury (TBI) or whiplash, carries a relevant burden on patients. PTH is still an undertreated condition because...
TL;DR: In this article, Fenfluramine has been shown to be a highly efficacious and safe treatment option for Dravet Syndrome patients, which is a severe developmental and epileptic encephalopathy.
Abstract: Introduction: Dravet Syndrome (DS) is a severe developmental and epileptic encephalopathy. Fenfluramine recently demonstrated to be a highly efficacious and safe treatment option for DS patients. F...
TL;DR: Increase the number of primary care medical services, spread the ‘headaches culture’ among GPs and ED doctors, the adoption of ICHD in the diagnostic protocols used in EDs and a fast referral to a headache center could decrease the inappropriate use of ED and improve the headache management in the emergency units.
Abstract: Introduction: Headache is the fifth most common reason to visit an emergency department (ED). In most of the cases, headache is benign and has a primary origin, with migraine as the most common dia...
TL;DR: Galvanic vestibular stimulation (GVS) is a non-invasive technique that activates vestibule afferents, influencing activity and oscillations in a broad network of brain regions as discussed by the authors.
Abstract: Introduction: Galvanic vestibular stimulation (GVS) is a noninvasive technique that activates vestibular afferents, influencing activity and oscillations in a broad network of brain regions. Several studies have suggested beneficial effects of GVS on motor symptoms in Parkinson's Disease (PD).Areas covered: A comprehensive overview of the stimulation techniques, potential mechanisms of action, challenges, and future research directions.Expert opinion: This emerging technology is not currently a viable therapy. However, a complementary therapy that is inexpensive, easily disseminated, customizable, and portable is sufficiently enticing that continued research and development is warranted. Future work utilizing biomedical engineering approaches, including concomitant functional neuroimaging, have the potential to significantly increase efficacy. GVS could be explored for other PD symptoms including orthostatic hypotension, dyskinesia, and sleep disorders.
TL;DR: In this article, a literature search was conducted using Pubmed search on the topics of drug-resistant Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin.
Abstract: Introduction Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin representing up to 10% of all epilepsy cases. Despite adequate anti-seizure medication (ASM) treatment, seizures persist in one-third of JME patients. Areas covered A literature search was conducted using Pubmed search on the topics of drug-resistant JME. Expert opinion About 30% of JME patients are drug-resistant. Valproate (VPA) is considered the first-choice drug. In women of childbearing potential, levetiracetam (LEV) should represent the first-choice treatment. Alternative monotherapy or add-on therapy should be considered in subjects with resistant seizures after the exclusion of pseudo-drug resistance. The choice of the add-on ASM depends on the predominant seizure type. In subjects with persistent bilateral tonic-clonic seizures, LEV or lamotrigine should be firstly considered. In patients with difficult-to-treat myoclonic seizures, clonazepam or LEV are recommended. In case of persistent absences, ethosuximide should be considered. With appropriate selection and safeguards in place, VPA should remain available as an option in women of childbearing potential whose seizures are resistant to other treatments.
TL;DR: Intranasal rescue drugs are a valuable treatment modality for seizure clusters and prolonged seizures that are effective and well tolerated with the potential to enhance patient quality of life, reduce the incidence of seizure-related injury, and lessen the need for hospital visits.
Abstract: Introduction Some people with epilepsy experience acute repetitive seizures (ARS), also termed seizure clusters, which have a negative impact on patient and caregiver quality of life, emotional wellbeing, daily function, and may pose risk of injury or death. In addition, these events increase healthcare utilization in emergency departments and hospitals, which might be avoided with use of an at-home rescue medication. Intranasal formulations of benzodiazepines used as rescue medications provide a means of delivering rescue medication that is socially acceptable and more easily administered than rectal drug. Areas covered This article provides a review of intranasal diazepam covering development, pharmacokinetics, dosing, safety, adverse effects, and efficacy. The authors compare it with rectal diazepam and intranasal midazolam. Expert opinion Intranasal rescue drugs are a valuable treatment modality for seizure clusters and prolonged seizures that are effective and well tolerated with the potential to enhance patient quality of life, reduce the incidence of seizure-related injury, and lessen the need for hospital visits. The literature does not provide evidence comparing the various rescue agents, and head-to-head comparison studies are needed. An inhaled benzodiazepine as a seizure rescue drug is currently undergoing clinical trials.
TL;DR: In this paper, the authors investigated the effect of the Covid-19 pandemic on MS patients' treatment, access to health care services and mental health, and provided evidence-based advice to ensure them a high standard of care even during the pandemic.
Abstract: Introduction Covid-19 has been sweeping over the world for more than a year. People with Multiple Sclerosis (MS) might be particularly vulnerable either for the disease iteself or for the ongoing immune treatment. The aim of this review is to understand the impact of the Covid-19 pandemic and lockdown on patients with MS and to provide evidence-based advice to ensure them a high standard of care even during the pandemic. Areas covered Literature search was conducted in the Scopus, Web of Science, Pubmed electronic databases, and articles reference lists to investigate the effect of Covid-19 on MS patients' treatment, access to health-care services and mental-health.The search terms 'multiple sclerosis' AND 'Covid-19' were combined with each of the following term 'disease modifying treatment,' 'steroids,' 'vaccination,' 'mental health,' 'stress,' 'quality of life,' 'management,' 'impact,' 'recommendations,'. Expert opinion To ensure MS control during the pandemic, minimizing the risk of Covid-19 contagion, face-to-face visits may be implemented with televisits. Management of relapses and DMTs schedule should be adapted based on the specific benefit/risk ratio for each patient, considering disease activity, disability, comorbidities. Vaccination should be strongly recommended. Telerehabilitation and online psychological support programs should be encouraged to preserve motor performances and mental health.
TL;DR: A review of the most promising therapies under study and the ongoing/planned clinical trials for Charcot-Marie-Tooth disease (CMT) and related neuropathies can be found in this article.
Abstract: Introduction: Charcot-Marie-Tooth disease (CMT) and related neuropathies represent the most prevalent inherited neuromuscular disorders. Nonetheless, there is still no pharmacological treatment available for any CMT type. However, the landscape is rapidly evolving and several novel approaches are providing encouraging results in preclinical studies and leading to clinical trials.Areas covered: The authors review the most promising therapies under study and the ongoing/planned clinical trials. Several approaches to address PMP22 overexpression underlying CMT1A, the most frequent subtype, are being tested. Gene silencing, targeting PMP22, and gene therapy, to introduce specific genes or to substitute or modulate defective ones, are being experimented in animal models. Compounds acting on ER stress, unfolded protein response, neuregulin pathways, phosphoinositides metabolism, axonal transport and degeneration, inflammation, polyol pathway, deoxysphingolipid metabolism, purine nucleotide pool are potential therapeutic candidates for different forms of CMT and related neuropathies.Expert opinion: We are getting closer to find effective therapies for CMT, but are far behind the exciting examples of other genetic neuromuscular disorders. The authors analyze the possible reasons for this gap and the way to fill it. Preclinical and clinical research is ongoing with coordinated efforts and they are confident that in the next few years we will see the first effective treatments.
TL;DR: Nabiximols, a cannabinoid-based oromucosal spray, is indicated as add-on therapy for symptomatic relief of spasticity in persons with multiple sclerosis (MS) as discussed by the authors.
Abstract: Introduction: Nabiximols, a cannabinoid-based oromucosal spray, is indicated as add-on therapy for symptomatic relief of spasticity in persons with multiple sclerosis (MS). This review compiles tol...