Expert Review of Neurotherapeutics最新文献

Introduction: Infantile epileptic spasms syndrome (IESS) is a common developmental and epileptic encephalopathy with poor long-term outcomes. A substantial proportion of patients with IESS have a potentially surgically remediable etiology. Despite this, epilepsy surgery is underutilized in this patient group. Some surgically remediable etiologies, such as focal cortical dysplasia and malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), are under-diagnosed in infants and young children. Even when a surgically remediable etiology is recognised, for example, tuberous sclerosis or focal encephalomalacia, epilepsy surgery may be delayed or not considered due to diffuse EEG changes, unclear surgical boundaries, or concerns about operating in this age group.

Areas covered: In this review, the authors discuss the common surgically remediable etiologies of IESS, their clinical and EEG features, and the imaging techniques that can aid in their diagnosis. They then describe the surgical approaches used in this patient group, and the beneficial impact that early epilepsy surgery can have on developing brain networks.

Expert opinion: Epilepsy surgery remains underutilized even when a potentially surgically remediable cause is recognized. Overcoming the barriers that result in under-recognition of surgical candidates and underutilization of epilepsy surgery in IESS will improve long-term seizure and developmental outcomes.

Introduction: The longitudinal course of bipolar disorder (BD) is associated with an active process of neuroprogression, characterized by structural brain alterations and progressive functional impairment. In the last decades, a growing need of a standardized staging model for BD arose, with the aim of a more appropriate definition of stage-specific clinical manifestations and the identification of more customized therapeutic tools.

Areas covered: The authors review the literature on clinical aspects, neurobiological correlates and treatment issues related to BD progression. Thereafter, they address the definition, constructs, and evolution of the staging concept, focusing on the clinical applications of BD staging models available in literature.

Expert opinion: Although several staging models for BD have been proposed to date, their application in clinical practice is still relatively scant. This may have a detrimental impact on the clinical and therapeutic management of BD, in terms of early and proper diagnosis as well as tailored treatment interventions according to the different stages of illness. Future research efforts should tend to the integration of recent insights on neuroimaging and epigenetic markers, toward a standardized and multidimensional staging model.

Introduction: Cholinesterase inhibitors, along with memantine, are the mainstay of symptomatic treatment for AD (Alzheimer's disease); however, these medications are typically administered orally, which can be difficult for people with AD and their caregivers.

Areas covered: In this drug profile and narrative review, the authors trace the development of the new FDA-approved transdermal donepezil. The authors discuss the studies showing its bioequivalence with the oral formulation, including two double-blinded placebo controlled non-inferiority trials. The authors also compare the patch to the only other transdermal cholinesterase inhibitor on the market, rivastigmine, and highlight the potential advantages and disadvantages between these two treatments.

Expert opinion: While the patch is bio-equivalent, it is rather large and may not be affordable for some patients. In addition, there is no high dose (e.g. 23 mg) equivalent. Nevertheless, transdermal donepezil will be useful for people with AD and their caregivers, given its effectiveness and potential convenience.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disorder with a fatal outcome 3-5 years after disease onset due to respiratory complications. Superoxide dismutase 1 (SOD1) mutations are found in about 2% of all patients. Tofersen is a novel oligonucleotide antisense drug specifically developed to treat SOD1-ALS patients.

Areas covered: Our review covers and discusses tofersen pharmacological properties and its phase I/II and III clinical trials results. Other available drugs and their limitations are also addressed.

Expert opinion: VALOR study failed to meet the primary endpoint (change in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to week 28, tofersen arm vs. placebo), but a significant reduction in plasma neurofilament light chain (NfL) levels was observed in tofersen arm (60% vs. 20%). PrefALS study has proposed plasma NfL has a potential biomarker for presymptomatic treatment, since it increases 6-12 months before phenoconversion. There is probably a delay between plasma NfL reduction and the clinical benefit. ATLAS study will allow more insights regarding tofersen clinical efficacy in disease progression rate, survival, and even disease onset delay in presymptomatic SOD1 carriers.

Introduction: Sleep disorders represent an important comorbidity in individuals with ADHD. While the links between ADHD and sleep disturbances have been extensively investigated, research on the management of sleep disorders in individuals with ADHD is relatively limited, albeit expanding.

Areas covered: The authors searched PubMed, Medline, PsycInfo, Embase+Embase Classic, Web of Sciences databases, and clinicaltrials.gov up to 4 January 2024, for randomized controlled trials (RCTs) of any intervention for sleep disorders associated with ADHD. They retained 16 RCTs (eight on pharmacological and eight on non-pharmacological interventions), supporting behavioral intervention and melatonin, and nine ongoing RCTs registered on clinicaltrials.gov.

Expert opinion: The pool of RCTs testing interventions for sleep disorders in individuals with ADHD is expanding. However, to inform clinical guidelines, there is a need for additional research in several areas, including 1) RCTs based on a precise phenotyping of sleep disorders; 2) pragmatic RCTs recruiting neurodevelopmental populations representative of those seen in clinical services; 3) trials testing alternative interventions (e.g. suvorexant or light therapy) or ways to deliver them (e.g. online); 4) sequential and longer-term RCTs; 5) studies testing the impact of sleep interventions on outcomes other than sleep; 6) and implementation of advanced evidence synthesis and precision medicine approaches.

Introduction: Essential tremor (ET) is the most frequent movement disorder, affecting up to 5% of adults > 65 years old. In 30-50% of cases, optimal medical management provides insufficient tremor relief and surgical options are considered. Thalamotomy is a time-honored intervention, which can be performed using radiofrequency (RF), stereotactic radiosurgery (SRS), or magnetic resonance-guided focused ultrasounds (MRgFUS). While the latter has received considerable attention in the last decade, SRS has consistently been demonstrated as an effective and well-tolerated option.

Areas covered: This review discusses the evidence on SRS thalamotomy for ET. Modern workflows and emerging techniques are detailed. Current outcomes are analyzed, with a specific focus on tremor reduction, complications and radiological evolution of the lesions. Challenges for the field are highlighted.

Expert opinion: SRS thalamotomy improves tremor in > 80% patients. The efficacy appears comparable to other modalities, including DBS, RF and MRgFUS. Side effects result mostly from idiosyncratic hyper-responses to radiation, which occur in up to 10% of treatments, are usually self-resolving, and are symptomatic in < 4% of patients. Future research should focus on accumulating more data on bilateral treatments, collecting long-term outcomes, refining targeting, and improving lesion consistency.

Introduction: Post-traumatic stress disorder (PTSD) is a disabling psychiatric condition with a worldwide prevalence between 6% and 9%, and more common in the female than in the male sex. The aim of this paper is to review and comment on the different factors that might explain the discrepancies in the pharmacological management of women and men.

Areas covered: The available literature shows that there exists a vulnerability of women to develop PTSD that may depend on neurobiological as well as environmental/cultural factors. These variables might influence the clinical picture, the outcome and the response to specific treatments, given their consequences on the pharmacokinetics of commonly prescribed drugs. Women suffering from PTSD are more prone to consult and receive more prescriptions of psychotropic drugs than men. However, it is evident that the particular stages of a women's life such as pregnancy or breastfeeding might require a specific evaluation and care.

Expert opinion: It is necessary to explore the pharmacokinetics of compounds highlighting sex-related differences, and their safety during pregnancy and lactation. Taking care of differences between women and men should represent a main focus of research, while being a primary target towards a really tailored pharmacological treatment of PTSD.