Therapeutic Advances in Neurological Disorders

Nerve decompression for diabetic peripheral neuropathy with nerve entrapment: a narrative review
Liao C and Zhang W
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes which primarily affects the sensory nervous system. Pain is the most common complaint that prompts patients to seek medical advice. With various presentations and intricate pathological mechanisms, diabetic peripheral neuropathic pain is currently the most crucial and challenging aspect of managing diabetic complications. As a heterogeneous disorder, there is no medication or treatment modality that is effective for all types of DPN and its associated neuropathic pain. Peripheral nerve decompression provides a new option for treating patients with diabetic peripheral neuropathic pain in the lower extremities. However, the clinical applicability of nerve decompression has been debated since it was first proposed. This review discusses the theoretical basis of nerve decompression, the clinical indications, and the progress of basic research based on the pathological mechanisms and nerve impairment patterns of diabetic peripheral neuropathic pain. The heterogeneity of DPN patients is summarized in terms of three aspects: complex pathophysiological mechanisms, multilevel nervous system involvement, and various nerve impairment properties. Identifying the presence of nerve entrapment among complex pathophysiological mechanisms is the key to successful outcomes. Tinel signs, focal pain, mechanical allodynia, and two-point discrimination were reported to be prognostic factors for good surgical outcomes, and their predictive ability might stem from their association with the early stage of entrapment neuropathy.
Optimizing outcomes in drug-resistant mesial temporal lobe epilepsy patients undergoing stereoelectroencephalography-guided radiofrequency thermocoagulation
Jean S, Jiang R, Dai Y, Chen W, Liu W, Deng D, Tagu PT, Wei X, Chen S, Fang X and Song S
Mesial temporal lobe epilepsy (MTLE) epileptiform discharges have been reported to arise from the hippocampus or the extrahippocampal medial temporal cortex, such as the amygdala, and then propagate to the temporal lobe cortex. The surgical ablation of which of these structures would result in a better postoperative outcome is debatable.
Possible clinical and radiological predictors of haemorrhagic transformation in acute stroke patients undergoing dual antiplatelet therapy: a clinical study
Bagnato MR, Maestrini I, Bruno L, Ciullo I, D'Agostino F, Lacidogna G, Marrama F, Mascolo AP, Rocco A and Diomedi M
The predictors of intracranial haemorrhagic transformation (HT) in acute ischaemic stroke (AIS) patients undergoing dual antiplatelet therapy (DAPT) are not well known.
Personality traits in patients with multiple sclerosis: their association with nicotine dependence and polypharmacy
Meißner J, Frahm N, Hecker M, Langhorst SE, Mashhadiakbar P, Streckenbach B, Burian K, Baldt J, Heidler F, Richter J and Zettl UK
The modifiable risk factor exerting the most substantial influence on the development and disease course of multiple sclerosis (MS) is cigarette smoking. Furthermore, smoking is associated with a higher risk of suffering from one or more comorbidities and potentially contributes to polypharmacy. We aimed to use personality tests to explore health-promoting and harmful patient characteristics.
Patient-reported treatment satisfaction in essential tremor: levels of satisfaction and predictors of satisfaction
Varghese A, Berry DS, Ghanem A, Hernandez NC and Louis ED
Although managing symptoms is paramount for both essential tremor (ET) patients and their healthcare providers, studies of treatment satisfaction are surprisingly lacking.
Short delay to initiate plasma exchange or immunoadsorption as synergistic therapies for patients in the acute phase of anti-NMDAR encephalitis
Su M, Wu Z, Luo Q, Feng H and Zhou H
Combined first-line therapies have been frequently adopted for patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Plasma exchange (PE) or immunoadsorption (IA) was used as an add-on option following initial immunotherapies, including high-dose steroids and intravenous immunoglobulin (IVIG). However, whether a shorter delay of PE or IA can improve the early recovery prognosis of patients with anti-NMDAR encephalitis remains largely unknown.
Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment
Kantorová E, Vítková M, Martiníková M, Cimprichová A, Fedicˇová M, Kovácˇová S, Mako M, Cisár J, Hancˇinová V, Szilasiová J, Koleda P, RoháIˇová J, Polóniová J, Karlík M, Slezáková D, Klímová E, Maciak M, Kurcˇa E and Hnilicová P
Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment.
Thrombectomy for patients with a large infarct core: a study-level meta-analysis with trial sequential analysis
Jhou HJ, Yang LY, Chen PH and Lee CH
The effectiveness and safety of endovascular treatment compared with medical management alone regarding outcomes for patients with a large infarct core remain uncertain.
The impact of different lifestyle factors on disability in multiple sclerosis at older ages: a monocentric retrospective study
Wecker S, Freudenstein D, Ganser I, Angstwurm K, Lee DH and Linker RA
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system affecting approximately 2.8 million people worldwide. In addition to genetic and environmental factors, various lifestyle factors contribute to disease development and progression.
Link between post-stroke psychopathology and scope-of-action awareness
Stahl B, Becker K, Kocyigit K, Denzler P and Röder P
Epidemiological research has failed to confirm laterality of lesion site as a neurobiological source of post-stroke psychopathology. However, acquired communication disorders have proved to be a key risk factor for depression, apart from established parameters such as pre-stroke psychopathology and physical immobility.
SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis
Montalban X, Rodriguez-Acevedo B, Nos C, Resina M, Forner M, Wu Y and Chirieac M
Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.
Bacterial signature in retrieved thrombi of patients with acute ischemic stroke-a systematic review
Zarrintan A, Ghozy S, Thirupathi K, Walden K, Brinjikji W, Kallmes DF and Kadirvel R
Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS.
The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study
Levitz D, Chao Foong Y, Sanfilippo P, Spelman T, Rath L, Roldan A, Lal A, Monif M, Jokubaitis V, Ozakbas S, Alroughani R, Boz C, Terzi M, Kalincik T, Blanco Y, Foschi M, Surcinelli A, Buzzard K, Skibina O, Laureys G, Van Hijfte L, Ramo-Tello C, Soysal A, Sanchez-Menoyo JL, Habek M, Cartechini E, Rojas JI, Karabudak R, Willekens B, Al-Harbi T, Fragoso Y, Castillo-Triviño T, Decoo D, Aragon de Vecino MC, Skromne E, Sirbu CA, Zhu C, Merlo D, Gresle M, Butzkueven H and Van Der Walt A
The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.
Cerebral air embolism following a hemodialysis session successfully treated with hyperbaric oxygen: a case report
Bousbaa A, Renou M, Poulain C, Laurent P, El Esper N, Choukroun G and Caillard P
We describe here the first case of cerebral air embolism (CAE) due to a dysfunctional long-term central venous catheter for hemodialysis in a 39-year-old woman with a history of lung transplantation. Air emboli are rare but potentially fatal complications of hemodialysis, in particular, when they involve the brain. Early management with hyperbaric oxygen therapy (HBOT) is critical to prevent deterioration of the patient's condition. In this case, our patient presented her first symptoms, likely a seizure due to multiple cerebral air emboli, during her hemodialysis session. She was then monitored in the Nephrology Intensive Care Unit in accordance to the medical reference center (with HBOT). Twelve hours later, she experienced secondary deterioration, presenting with acute aphasia, left hemineglect syndrome, and hemiplegia. She was rapidly transferred to the medical reference center for HBOT. The patient fully recovered after receiving three sessions of HBOT. She also presented a seizure during each HBOT session, attributed to hyperoxia. She never experienced another seizure after the episode of CAE. This case highlights the importance of considering patients who have a lung transplant to be at increased risk for air emboli during hemodialysis and the need to rapidly recognize symptoms and start treatment, including HBOT, to optimize recovery.
Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management
Oreja-Guevara C, Martínez-Yélamos S, Eichau S, Llaneza MÁ, Martín-Martínez J, Peña-Martínez J, Meca-Lallana V, Alonso-Torres AM, Moral-Torres E, Río J, Calles C, Ares-Luque A, Ramió-Torrentà L, Marzo-Sola ME, Prieto JM, Martínez-Ginés ML, Arroyo R, Otano-Martínez MÁ, Brieva-Ruiz L, Gómez-Gutiérrez M, Rodríguez-Antigüedad A, Galán Sánchez-Seco V, Costa-Frossard L, Hernández-Pérez MÁ, Landete-Pascual L, González-Platas M and Meca-Lallana JE
Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS.
Long-term analysis of infections and associated risk factors in patients with multiple sclerosis treated with ocrelizumab: pooled analysis of 13 interventional clinical trials
Derfuss T, Bermel R, Lin CJ, Hauser SL, Kappos L, Vollmer T, Comi G, Giovannoni G, Hartung HP, Weber MS, Wang J, Jessop N, Chognot C, Craveiro L and Bar-Or A
Patients with multiple sclerosis (PwMS) have an increased risk of infections.
Therapeutic effect of an inhaled levodopa dry powder formulation on off episodes in patients with Parkinson's disease
de Jong L, Luinstra M, Aalbers AF, Wijma-Vos AJ, D'Angremont E, van der Meulen AAE, Rutgers AWF, Steenhuis L, Hagedoorn P, van Laar T and Frijlink HW
Limited treatment options with a rapid onset of action are available to treat off episodes in Parkinson's disease (PD) patients. Therefore, the development of rapid onset formulations, for instance with levodopa, is warranted, which was the reason to investigate an inhalable formulation of levodopa.
Clinical and ethical challenges in decision-making for patients with disorders of consciousness and locked-in syndrome from Chinese neurologists' perspectives
Li M, Yan Y, Kuehlmeyer K, Huang W, Laureys S and Di H
The diagnosis of and life-sustaining treatment (LST) for patients with disorders of consciousness (DoC) and locked-in syndrome (LIS) have been the subject of intense debate.
Lower leukocytes pretreatment as a possible risk factor for therapy-induced leukopenia in interferon-beta-treated patients with multiple sclerosis
Protopapa M, Schmaul S, Schraad M, Pape K, Zipp F, Bittner S and Uphaus T
Interferon-beta (IFN-β) still plays a fundamental role in immunomodulation of people with multiple sclerosis (MS) with low disease activity and in clinically isolated syndrome (CIS). In 2014, pegylated (PEG) interferon was licensed by the European Medicines Agency (EMA) for relapsing-remitting MS (RRMS), enabling a lower dosing frequency.
Effects of visual feedback balance system combined with weight loss training system on balance and walking ability in the early rehabilitation stage of stroke: a randomized controlled exploratory study
Lu W, Wen M, Li Y, Liu F, Li Y, Zhang H and Zhang M
Previous studies have suggested that the Pro-Kin visual feedback balance system can promote the recovery of balance function in stroke patients.
Clinical and radiological implications of subpotent generic fingolimod in multiple sclerosis: a case series
Okuda DT, Tardo LM, Wright CM, Munoz SB, Punnen TG, Patel MA, Moog TM and Burgess KW
An expansion in the availability of generic specialty disease modifying therapies (DMTs) for treatment of multiple sclerosis (MS) has increased recently. Generic specialty medications aim to provide greater access to molecules that alter the disease trajectory at lower costs. The US Food and Drug Administration requires generic products to contain between 90% and 110% of the stated active ingredient and an 80%-125% bioequivalence range. We present the clinical experiences and absolute lymphocyte counts (ALC) trends of six people with MS originally treated with Gilenya (fingolimod) 0.5 mg who were required to transition to generic fingolimod 0.5 mg by third-party administrators, and the medication content from recovered products. Six individuals with acute clinical exacerbations or disease advancement on MRI were identified during routine scheduled visits from a tertiary care center and consecutively included from January 2024 to August 2024. ALC trends were constructed for each individual during Gilenya and generic fingolimod treatment. These individuals experienced signs of disease advancement while on generic fingolimod 0.5 mg at approximately 1 year of treatment and elevations in ALC, a biological metric related to the mechanism of action of sphingsine-1-phosphate receptor modulation, were observed following the transition. High purity fingolimod for standardization tests, Gilenya 0.5 mg, and five recovered generic fingolimod 0.5 mg products were independently tested in an accredited laboratory. Gilenya 0.5 mg capsules had an average fingolimod content of 97.7% (standard deviation (SD) = 2.59%). Three recovered generic fingolimod 0.5 mg products used during relapses had an average content of 91.2% (3.25%), 81.6% (6.24%), and 72.5% (2.05%). Two generic fingolimod 0.5 mg products not associated with relapse activity revealed averages of 97.4% (1.82%) and 103.3% (3.77%). Subpotent generic specialty DMTs may not only result in greater risk for disease activity but may also expose individuals to the potential for disease rebound, depending on the mechanism of action.