Current Neurology and Neuroscience Reports最新文献

Purpose of review: The objective of this review is to provide a comprehensive management protocol for the treatment of intracranial pressure (ICP) crises based on the latest evidence.

Recent findings: The review discusses updated information on various aspects of critical care management in patients experiencing ICP crises, including mechanical ventilation, fluid therapy, hemoglobin targets, and hypertonic saline infusion, the advantages of ICP monitoring, the critical ICP threshold, and bedside neuromonitoring. All aspects of critical care treatment, including hemodynamic and respiratory support and adjustment of ICP reduction therapy, may impact patient outcomes. ICP monitoring allows ICP values, trends, waveforms, and CPP calculation, which are helpful to guide patient care. Advanced neuromonitoring devices are available at the bedside to diagnose impaired intracranial compliance and intracranial hypertension, assess brain function, and optimize cerebral perfusion. Future research should focus on developing appropriate intervention protocols for both invasive and noninvasive neuromonitoring in managing ICP crisis patients.

Purpose of review: To describe recent research relevant to factors which predispose to giant cell arteritis (GCA) and those which trigger its manifestation, with particular emphasis on the more recent and controversial associations (COVID-19, vaccination, novel medications) which have changed the medical landscape and perhaps GCA prevalence.

Recent findings: GCA remains more prevalent in Caucasians but nevertheless affects other racial groups. Certain HLA haplotypes (i.e. DRB1*04) incurs risk of GCA. Polymyalgia rheumatica remains a strong association, and recent evidence also associates GCA with hematologic malignancy. COVID-19 infection may trigger GCA, in addition to vaccination (particularly the COVID-19 vaccine) and reactivated VZV infection, though the latter may be related to a common trigger. PD1-inhibitors may be associated with GCA. Previously establish patterns in geography and latitude are supported. A seasonal pattern of GCA in the summer/spring months is suggested but not proven. Controversy regarding GCA risk factors exists, as well as to whether the overall prevalence of GCA is rising. Given the growing aging population, the total number of cases of GCA will certainly increase, a challenge to which that our healthcare system must continue to rise to meet.

Purpose of review: Discuss the current understanding of the pathophysiology and management of refractory trigeminal neuralgia (TN). This includes a discussion on why TN can recur after microvascular decompression and a discussion on "outside of the box" options when both first- and second-line management strategies have been exhausted.

Recent findings: This review discusses second- and third-line oral medication options, botulinum toxin A, repeat microvascular decompression, repeat ablative procedures, internal neurolysis, trigeminal branch blockade, and neuromodulation using TMS or peripheral stimulation. Additional management for chronic neuropathic facial pain such as deep brain stimulation, motor cortex stimulation, and focused ultrasound thalamotomy are also discussed, though evidence in trigeminal neuralgia is limited. Treatment of recurrent TN despite multiple surgeries can be challenging, and multiple minimally invasive and more invasive management options have been reported in small studies and case reports. Further studies are needed to determine an optimal stepwise approach.

Purpose of review: To review the management of Idiopathic Intracranial Hypertension (IIH) with co-existing conditions affecting therapy: obesity, sulfa allergy, nephrolithiasis, and pregnancy.

Recent findings: The IIH-WT trial showed that bariatric surgery is currently the most effective method for obese patients with IIH to lose weight, leading to normalization of CSF pressure in many cases. Allergy to sulfonamide antibiotics does not preclude the use of acetazolamide; rather, penicillin allergy or multiple drug allergies are the strongest predictor of a hypersensitivity reaction. Carbonic anhydrase inhibitors should be avoided in individuals with a personal history of nephrolithiasis; the risk of renal stones increases with concomitant use of other medications with the potential for nephrolithiasis. Glucagon-like peptide-1 receptor antagonists (GLP-1RA) are promising non-surgical weight loss options although preliminary studies have not demonstrated considerable impact on papilledema, headache or vision. Women with IIH have high rates of pregnancy complications partly related to obesity. Recommendations for weight gain or loss during gestation are controversial. Recent studies show better outcomes in obese women who maintain or lose weight while pregnant including gestational diabetes, pre-eclampsia and emergency caesarian section. Progress continues in the search for the cause and best treatments for IIH. Larger multicenter trials of GLP-1RA are needed to determine their efficacy.

Purpose of the review: Preclinical and clinical evidence support the notion that neurodevelopmental disorders (NDDs) are synaptic disorders, characterized by excitatory-inhibitory imbalance. Despite this, NDD drug development programs targeting glutamate or gamma-aminobutyric acid (GABA) receptors have been largely unsuccessful. Nonetheless, recent drug trials in Rett syndrome (RTT), fragile X syndrome (FXS), and other NDDs targeting other mechanisms have met their endpoints. The purpose of this review is to identify the basis of these successful studies.

Recent findings: Despite increasing evidence of disruption in synaptic homeostasis, most genetic variants associated with NDDs implicate proteins involved in cell regulation and not in neurotransmission. Metabolic processes, in particular mitochondrial function, appear to play a role in NDD pathophysiology. NDDs are also characterized by distinctive cell signaling abnormalities, which link cellular and synaptic homeostasis. Recent successful trials in NDDs, including those of trofinetide, the first drug specifically approved for one of these disorders (i.e., RTT), implicate the targeting of downstream processes (i.e., signaling pathways) rather than neurotransmitter receptors. Recent positive drug studies in NDDs and their underlying mechanisms, in conjunction with new knowledge on the pathophysiology of these disorders, support the concept that targeting signaling and cellular and synaptic homeostasis may be a preferred approach for ameliorating synaptic abnormalities in many NDDs.

Purpose of review: Advancements in precision medicine have shifted the treatment paradigm of brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer, and melanoma, especially through targeted therapies focused on specific molecular drivers. These novel agents have improved outcomes by overcoming challenges posed by the blood-brain barrier (BBB) and resistance mechanisms, enabling more effective treatment of BM.

Recent findings: In NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies. In HER2-positive breast cancer, significant advancements with tucatinib and trastuzumab deruxtecan (T-DXd) have transformed the treatment landscape, achieving improved survival and intracranial control in patients with BM. Similarly, in triple-negative breast cancer (TNBC), novel therapies such as sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) offer new hope for managing BM. For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases. Developing targeted therapies penetrating the BBB has revolutionized BM treatment by targeting key drivers like EGFR, ALK, HER2, and BRAF. Despite improved survival, challenges persist, particularly for patients with resistant genetic alterations. Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.

Purpose of review: To evaluate the role of sedation vacations in optimizing patient outcomes and enhancing the quality of care in neurological intensive care units (ICUs). We discuss the importance of sedation management in neurocritical care, considering recent research findings and clinical guidelines.

Recent findings: Recent studies have highlighted the significance of sedation interruption protocols in improving patient outcomes in the ICU setting. Evidence suggests that daily sedation interruptions can reduce the duration of mechanical ventilation, ICU length of stay, and mortality rates. However, the implementation of these protocols requires careful consideration of patient-specific factors and a multidisciplinary approach. Sedation vacations play a critical role in neurocritical care by reducing mechanical ventilation duration, ICU stay length, and mortality rates. Despite the benefits, the presence of complications must be addressed to avoid adverse outcomes. Continued research is necessary to refine these strategies and improve guideline quality, ensuring safe and effective sedation management in critically ill neurological patients.

Purpose of review: Postoperative delirium (POD) is a common complication that has important implications for surgical patients, often leading to both short- and long-term cognitive deficits, worse outcomes, and increased healthcare costs. Given these implications, there may be a benefit in reducing the incidence of POD. Pharmacologic interventions may have the potential to reduce the risk of a patient developing POD.

Recent findings: Recently studied therapies include dexmedetomidine, propofol, haloperidol, ketamine, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, acetaminophen, melatonin/ramelteon, corticosteroids, midazolam, physostigmine, and neostigmine. In addition, the implementation of regional anesthesia and reduction of overall anesthetic depth have been examined. Of these therapies, dexmedetomidine has been studied the most and has the most supporting evidence for prevention of POD, but current studies lack clarity on optimal dosing and timing of dexmedetomidine administration. Acetaminophen, corticosteroids, and melatonin/ramelteon are other plausible medications that have potential for reducing POD incidence, but they all require further investigation. Reduction of anesthetic depth and regional anesthetics are options for anesthetic management that show promise but still lack enough supporting evidence in recent literature to receive a strong recommendation. Future research should focus on identifying optimal strategies for the implementation of the pharmacological options listed, including doses and timing of administration. Attention should be given to dexmedetomidine given its promise demonstrated by recent literature.

Purpose of review: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive form of lymphoma that can involve the brain, spinal cord, leptomeninges and eyes. PCNSL prognosis continues to be poor, with 5-year survival rates of 30-40%. Therapeutic options are especially limited for relapsed/refractory (r/r) PCNSL. In recent years, studies shed light on the pathogenesis and oncogenic pathways driving PCNSL, leading to the development of novel therapeutics. In this review, we discuss the evidence supporting these novel agents and present ongoing clinical studies.

Recent findings: Key oncogenic drivers of PCNSL include activation of the NFkB pathway, cell cycle dysregulation, somatic hypermutation and immune evasion, leading to the investigation of targeted therapeutics and immunotherapeutics to inhibit these pathways. Such approaches include BTK inhibitors, mTOR/PI3K inhibitors, immunomodulatory agents (IMIDs), immune checkpoint inhibitors and CD19-based CAR T-cells. The therapeutic repertoire for PCNSL is rapidly evolving, and a multi-modality approach including intensive chemotherapy regimens and novel therapies will likely be utilized in the future.