Expert Review of Neurotherapeutics最新文献

Introduction: We present a literature review on the clinical conundrums surrounding the differential diagnosis of restless legs syndrome (RLS, Willis-Ekbom disease), as well as conditions that can mimic RLS. An extensive literature search showed that secondary causes of RLS ranged from commonly recognized causes, such as iron deficiency anemia, to less widely noted causes, such as rheumatoid disorders and hypothyroidism. There is a controversial association with Parkinson's disease, essential tremor, and RLS, whereby RLS is proposed as a prodromal feature.

Areas covered: The clinical presentation of restless legs syndrome (RLS), a highly prevalent movement disorder usually during sleep with a circadian variation. The review highlights differences between commonly established secondary causes of RLS, RLS mimics, genetic and drug-induced RLS. A flowchart presents some key features of different and overlapping secondary RLS and mimics and genetic RLS.

Expert opinion: RLS is one of the commonest movement disorders and the International Restless Legs Syndrome Study Group has suggested five-point criteria for robust diagnosis of RLS. However, even in expert hands, diagnosis is accurate in about 85% and misdiagnosis, especially with 'RLS mimics,' appears to be high. There are wide variations in the way RLS can present, and this includes different types of secondary RLS as well as drug induced or genetic patterns of RLS. Secondary RLS is highly complex and can be associated with Parkinson's disease as well as prodromal stage of Parkinson and essential tremor. Other known causes of secondary RLS are many and include end-stage kidney disease as well as metabolic disorders to painful conditions such as rheumatic disorders and fibromyalgia and polyradiculopathy.

Introduction: Somatostatin analogs (SSAs) were developed as antisecretory agents to palliate hormonal symptoms in patients with functioning neuroendocrine tumors (NETs). Their antiproliferative activity has been established in the phase 3 PROMID and CLARINET trials. SSAs currently represent the standard first-line therapy for the majority of well-differentiated G1/G2 gastroenteropancreatic NETs as well as for pulmonary NETs.

Areas covered: An update on the clinical applications of established SSAs for the treatment of NETs is provided. Perspectives on emerging nonpeptide SSAs such as paltusotine and innovative formulations of octreotide (CAM2029) are included.

Expert opinion: SSAs represent the cornerstone of treatment for both functioning and nonfunctioning NETs. While standard-dose SSAs have a defined place in the therapeutic algorithm of well-differentiated NETs, uncertainties remain on how to best integrate above-label doses of SSAs in the treatment sequence, particularly when tumor control is the goal. Octreotide and lanreotide appear to be clinically interchangeable, and no signs of superiority of one agent over the other has been observed so far. Whether SSAs may be exploited in the maintenance setting following more aggressive treatments, whether continuing SSAs beyond-progression after first-line therapy could be an effective treatment strategy, and whether new-generation SSAs such as pasireotide could overcome resistance to established SSAs are key areas of investigation.

Introduction: After a long period of obscurantism, a possible role of psychedelics in clinical practice has progressively become a tangible perspective during the last two decades. However, the resounding enthusiasm linked to such 'psychedelic renaissance' runs the risk to unduly minimize the possible hazards associated with these compounds, while expanding their alleged benefits to improbable panacea-like proportions. In order to avoid mystifying or demonizing the properties of 5-HT2a agonists on emotional grounds, this subject requires a strictly unprejudiced and cautious approach to the evidence.

Areas covered: In this article, the authors attempted to comprehensively analyze the available literature to provide a balanced overview of the possible benefits of psychedelics in healthcare, taking into account their potential risks.

Expert opinion: To date, psychedelics have shown a therapeutic potential in a wide range of conditions, with a seemingly limited risk of inducing adverse reactions, including abuse and dependence, when administered in a controlled environment by specialized personnel. In any case, although several questions remain unanswered before drawing firm conclusions, further studies are needed to establish which conditions and subjects could benefit from psychedelics and which patients bear the greater risk of adversities.

Introduction: Cognitive impairment in Parkinson's disease (PD) substantially affects patient outcomes, function, and quality of life. PD-related cognitive dysfunction is often heterogeneous in clinical presentation and rates of progression. As cognitive changes occur in many people with PD, it is essential to evaluate cognition, provide education, and implement management strategies for cognitive symptoms.

Areas covered: This article describes the symptomatology, epidemiology, risk factors, and pathobiology of cognitive impairment in PD. Additionally, the article provides an overview of evidence-based management and other therapeutic and coping strategies for cognitive impairment and dementia in PD. Comment is offered on challenges and opportunities for trials and emerging therapeutics targeting cognitive symptoms or decline.

Expert opinion: While our understanding of cognitive dysfunction in PD has grown, effective and safe therapeutics are still needed to not only treat cognitive impairment and dementia symptomatically but also slow down or prevent cognitive decline. Further research is needed to elucidate the pathobiology of PD cognitive impairment, develop validated biomarkers reflecting cognitive change, and ultimately, integrate clinical and biological frameworks. Consensus regarding cognitive evaluations, definitions, and criteria of cognitive impairment, evaluating functional abilities in the context of cognitive impairment, and determining optimal outcome measures for clinical trials remain unmet needs.

Introduction: Cognitive impairment (CI) occurs in 34-70% of multiple sclerosis (MS) patients, significantly impacting quality of life. CI can occur independently of physical disability, even in those with 'benign MS.' Cognitive deficits are heterogeneous, but common areas affected include processing speed, memory, and executive functions.

Areas covered: A comprehensive literature search was conducted across databases such as PubMed and Google Scholar, using keywords like 'MS,' 'cognition,' and 'cognitive rehabilitation.' We focused on clinical assessment tools, emerging cognitive phenotypes, and both pharmacological and non-pharmacological treatments, including disease-modifying therapies and cognitive rehabilitation techniques.

Expert opinion: Current evidence underscores the need for a multifaceted approach to managing CI in MS, incorporating emerging pharmacological treatments, cognitive rehabilitation strategies, and exercise programs. Future research should prioritize defining optimal training intensities, integrating therapies for sustained cognitive enhancement, and exploring neuromodulation and neuroimaging biomarkers within randomized controlled trials aimed at improving cognitive functioning in MS.

Introduction: Post-traumatic stress disorder (PTSD) can have debilitating effects on quality of life, and conventional treatments show mixed results. Neuromodulation is emerging as a promising approach for treating PTSD. This review examines current neuromodulatory treatments for PTSD, and highlights methodologies, clinical outcomes, and gaps in the literature to help guide future research.

Areas covered: A PubMed search identified 252 studies on PTSD and neuromodulation, of which 61 were selected for full review. These included 37 studies on repetitive transcranial magnetic stimulation (rTMS), 10 on transcranial direct current stimulation (tDCS),4 on deep brain stimulation (DBS) and 2 on focused ultrasound (FUS).

Expert opinion: The present review supports the potential of neuromodulation to reduce PTSD symptoms. rTMS and tDCS targeting the dlPFC appear effective through modulating neural circuits involved in fear processing and conditioning, however, literature varies regarding efficacy of stimulation frequencies and hemispheric targets. DBS targeting the amygdala or subcallosal cingulate white matter tracts improves treatment of refractory PTSD with sustained benefits, while FUS may improve symptoms through targeted modulation of brain structures such as the amygdala, though this technique is in the early stages of exploration. Future research should refine established neuromodulatory approaches and address gaps in emerging modalities to enhance treatment efficacy.

Introduction: Status epilepticus represents a significant neurological emergency, with high morbidity and mortality rates. In addition to standard care, the identification of adjuvant strategies is essential to improve the outcome.

Areas covered: The authors conducted a narrative review to provide an update on the value of hypothermia as an antiseizure and neuroprotective treatment in status epilepticus.

Expert opinion: The use of targeted temperature management in the treatment of hypothermia in patients with status epilepticus represents a potentially promising adjuvant strategy, supported by a substantial body of experimental evidence. However, further clinical data demonstrating its efficacy are necessary before it can be recommended for routine use in targeted patient populations, such as those with refractory or super-refractory status epilepticus.