Current Treatment Options in Neurology最新文献

Purpose of review

This review aims to provide a critical appraisal of current diagnostic and therapeutic strategies for patients with orbital inflammatory disease (OID). We present the reader with a review of clinical, imaging, laboratory, and biopsy based assessment of OID and review the current treatment modalities utilized including corticosteroids, corticosteroid-sparing (immunomodulatory) agents, radiation, antibiotics, and disease specific therapy.

Recent findings

Two major developments and trends have emerged in the management of orbital inflammation. First, improved understanding and distinction of inflammation subtypes (myositis, dacryoadenitis, or infiltrative) allows for more nuanced workup and treatment. Second, immunomodulatory agents have shown promise in achieving disease control in cases of truly idiopathic or corticosteroid-resistant OID. Together, these advances have led to fewer adverse effects and better efficacy.

Summary

The optimal treatment of OID depends on distinguishing between nonspecific and specific inflammation. Nonspecific inflammation tends to respond to corticosteroid therapy with a lower chance of relapse, while specific orbital inflammation often requires targeting the underlying disease with steroid-sparing therapy and immunomodulatory agents.

Purpose of review

This review describes risk factors for severe skin reactions to antiseizure medications (ASMs), the usage of updated tests to predict those with increased risk of a severe cutaneous reaction, and guides how to choose specific ASMs and dosing to lower the risk for these reactions. Information is given regarding specific mild versus severe reactions, initial diagnostic evaluation, and treatment. A table listing the risk of mild and severe cutaneous reaction risks as well as the management of potential seizures that may occur while stopping the culprit ASM are provided.

Recent findings

Five new ASMs have joined the total of 26 FDA-approved ASMs since 2018. Cenobamate had three patients develop a drug reaction with eosinophilia and systemic symptoms. A lower starting dosing and slower titration have resulted in no further published cases. Based on limited data, rash risk is low for fenfluramine, ganaxalone, and stiripentol. It is low-moderate for Epidiolex. Molecular tests can predict severe reactions.

Summary

Skin reactions are a relatively common side effect of ASMs with aromatic ASMs having the greatest risk. Identifying and informing high-risk patients when to seek medical attention, stopping the culprit ASM when a severe reaction looks possible, and providing appropriate medical triage can reduce morbidity and mortality from severe skin and systemic reactions.

Purpose of Review

Atypical parkinsonism is a term usually used to describe three neurodegenerative parkinsonian disorders: progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). In contrast to Parkinson’s disease, these disorders have a poor prognosis and present with a multitude of diverse symptoms, including parkinsonism, dystonia, myoclonus, gait disorders, dysarthria, dysphagia, sleep, cognitive, and behavioral disorders. In the absence of an approved disease-modifying treatment, symptomatic treatment is the mainstay of management. The purpose of this review is to present an overview of the management of these complex disorders, with a particular focus on a holistic and multidisciplinary approach.

Recent Findings

In addition to presenting the most significant pharmacological interventions for symptom management, data regarding non-pharmacological interventions are analyzed. Important non-pharmacological clinical practice questions such as breaking the news, palliative care, and end-of-life issues are discussed, in an effort to present an overview of the management of atypical parkinsonism from diagnosis to the most advanced stages of these diseases.

Summary

Management of atypical parkinsonian disorders includes symptomatic pharmacological and non-pharmacological interventions, in addition to addressing issues such as informing the patient of the diagnosis, palliative care, and end-of-life issues, which require a multidisciplinary approach.

Abstract

Purpose of Review

To care for patients with cerebrovascular disease (CVD), neurointerventionalists, intensivists, and other healthcare providers must be equipped to address associated ethical challenges. This review aims to delineate the applicability of fundamental bioethical approaches to CVD, highlight key ethical issues in CVD care, and delineate an ethical framework to streamline ethical decision-making for people with CVD.

Recent Findings

Three introductory cases are presented. The four key principles of principalism and the approach of narrative ethics are described with reference to CVD. Key ethical considerations include decision-making capacity and informed consent, uncertainty, and resource allocation. A categorization of CVD as emergent/nonemergent and the recommended management as intervention/no intervention helps frame the spectrum of CVD. A different six-pathway may then be taken based on which category the patient case corresponds to.

Summary

Physicians involved in the care of people with cerebrovascular disease must understand how the ethical issues manifest in individual patient cases to ensure appropriate care. The aforementioned ethical framework may aid physicians in providing ethically sound care. All decisions must involve a balance between clinical expertise and patient values and preferences or those articulated by a surrogate to properly respect the wishes of patients with CVD.

Purpose of Review

Bed rest was a treatment recommended for critically ill patients admitted to the intensive care unit (ICU) that aimed to minimize energy expenditure, permit wound healing and minimize somatic stressors. However, evidence demonstrates that bed rest leads to disuse atrophy, which may be compounded by premorbid sarcopenia and ICU-acquired weakness (ICUAW). ICUAW partly results from muscle breakdown and systemic inflammation and may exacerbate critical illness. Coupled with analgosedation, ICUAW may prolong mechanical ventilation (Kho et al. in BMJ Open Respir Res. 2019;6(1) 2019; Maffei et al. in Arch Phys Med Rehabil. 2017;98 2017; McWilliams et al. in J Crit Care. 2018;44 2018; Sarfati et al. in J Crit Care. 2018;46 2018), increase risk of venous thromboembolism (Denehy et al. in Intensive Care Med. 2017;43(1) 2017; Lyles in J Am Geriatr Soc. 1988;36(11) 1988) create dependence on vasopressor agents (Lyles in J Am Geriatr Soc. 1988;36(11) 1988; Fortney et al. in Comprehen Physiol. 1996) restrict joint mobility, and induce pressure injuries. Neurologically injured patients may be at a higher risk of ICUAW than other critically-ill patients, given that neurological injury itself results in weakness, which may be focal or generalized. Early mobilization (EM), typically defined as physical therapy within 72 h of ICU (Cumming et al. in Neurology. 2019;93(7) 2019), may preempt or mitigate these deleterious consequences of critical care.

Recent Findings

Retrospective data suggest that EM protocols reduce ventilator days, decrease venous thromboembolism, avert pressure wounds, and reduce the length of stay. EM may reduce the incidence, duration, and severity of delirium (Morris et al. in Crit Care Med. 2008;36(8) 2008; Needham et al. in Arch Phys Med Rehabil. 2010;91(4) 2010). Larger and more rigorous studies have not demonstrated benefit of EM on outcomes after critical care; some have demonstrated harm. Neurologically injured critical care patients have generally been excluded from early mobilization protocols due to safety concerns that stem from the increased potential for falls, disorders of consciousness, cognitive impairment, intracranial hypertension, and potential dislodgment of intracranial devices. Notably, data from patients with ischemic stroke suggest that EM may also be associated with harm in this group.

Summary

EM may benefit neurologically injured patients once acute ischemia, elevated ICP, and seizures are resolved. Targeting moderate acuity patients may be critical to improving outcomes and optimizing resource utilization in this resource-intensive intervention. The duration of mobility session, optimal frequency of mobility session, and timing of session remain to be determined.

Abstract

Purpose of Review

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing weakness, respiratory failure, and death within 3 to 5 years. Approximately, 10% of ALS cases have a genetic etiology (familial/fALS). The etiology of the remaining 90% of sporadic ALS (sALS) cases remains unknown. In this review, we provide an overview of approved and investigational therapies for fALS, as well as genetically informed therapeutic advances aimed at the larger sALS population.

Recent Findings

Antisense oligonucleotides (ASOs) are a promising strategy to treat toxic gain-of-function mutations underlying most forms of fALS. We discuss the recent approval of tofersen for ALS caused by mutation in SOD1. We also discuss progress in the development of therapies for fALS associated with C9orf72 hexanucleotide repeat expansions (C9orf72) and fused in sarcoma (FUS) mutations. Finally, we will discuss the rationale and status of molecular therapies for sALS targeting mediators of TDP-43 pathogenesis: ataxin-2 (ATXN2) and stathmin-2 (STMN2).

Summary

Advances in understanding the genetics of ALS have propelled the development of promising gene therapies. Lessons learned from tofersen continue to inform clinical trial design for a growing pipeline of therapies directed towards other fALS subtypes and sALS.

Purpose of Review

This article presents a summary of the new medications approved for generalized myasthenia gravis (gMG) since 2017. Pivotal clinical trials that led to the approval of these medications and their open-label extension studies are reviewed. We also provide information on healthcare cost when available. Lastly, we propose an approach to selecting therapies.

Recent Findings

Six new medications have been approved for acetylcholine receptor antibody positive gMG. These include the complement inhibitors eculizumab, ravulizumab, and zilucoplan and the neonatal Fc receptor blockers efgartigimod, efgartigimod and hyaluronidase, and rozanolixizumab. The latter is also approved for muscle-specific kinase gMG. The Myasthenia Gravis Activities of Daily Living (MG-ADL) has become the most commonly used primary outcome measure in gMG clinical trials.

Summary

All medications have shown safety and efficacy as measured by clinically meaningful changes in the MG-ADL. The medications differ in the need for meningococcal vaccination, the route and frequency of administration, and timing of treatments. Comparison studies are lacking and therefore there is limited evidence to guide the selection of therapy.

Purpose of review

This review describes the current approaches to the diagnosis and management of progressive supranuclear palsy (PSP)

Recent findings

PSP is an atypical parkinsonian disorder associated with the accumulation of abnormal 4-repeat tau protein in the brain. Initially, the recognized clinical phenotype included a progressive disorder with vertical supranuclear gaze palsy and prominent postural instability leading to early falls. However, the current PSP diagnostic criteria recognize a broader range of clinical PSP presentations and define eight clinical PSP variants according to the levels of diagnostic certainty. While definite PSP remains a neuropathological diagnosis, imaging modalities including brain magnetic resonance imaging (MRI), dopamine transporter (DAT), and tau positron emission tomography (PET) scans may aid in the diagnosis. In the future, new tau PET ligands and CSF and genetic biomarkers may improve diagnostic accuracy. There is no disease-modifying therapy currently available for PSP. However, there are many pharmacological and non-pharmacological treatment options for symptomatic management. Because PSP is a multisystem disease, optimal management requires a coordinated multidisciplinary team approach.

Summary

PSP is a fatal multisystem disease that can be challenging to diagnose and manage. However, improved clinical diagnostic criteria, emerging biomarkers, and availability of useful therapeutic approaches provide cause for optimism.