Managing cognitive impairment in Parkinson’s disease: an update of the literature

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: Jan. 7, 2025

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

Language: Английский

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PET brain imaging in neurological disorders

Physics of Life Reviews, Journal Year: 2024, Volume and Issue: 49, P. 100 - 111

Published: March 24, 2024

Language: Английский

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Recent advances of focused ultrasound induced blood-brain barrier opening for clinical applications of neurodegenerative diseases

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 209, P. 115323 - 115323

Published: April 21, 2024

Language: Английский

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An Overview on the Physiopathology of the Blood–Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(7), P. 849 - 849

Published: June 22, 2024

The state of well-being and health our body is regulated by the fine osmotic biochemical balance established between cells different tissues, organs, systems. Specific districts human are defined, kept in correct functioning, and, therefore, protected from exogenous or endogenous insults both mechanical, physical, biological nature presence barrier In addition to placental barrier, which even acts as a linker two organisms, mother fetus, all barriers, including blood-brain (BBB), blood-retinal blood-nerve blood-lymph blood-cerebrospinal fluid operate maintain physiological homeostasis within tissues organs. From pharmaceutical point view, most challenging undoubtedly BBB, since its notably complicates treatment brain disorders. BBB action can impair delivery chemical drugs biopharmaceuticals into brain, reducing their therapeutic efficacy and/or increasing unwanted bioaccumulation surrounding healthy tissues. Recent nanotechnological innovation provides advanced biomaterials ad hoc customized engineering functionalization methods able assist brain-targeted drug delivery. this context, lipid nanocarriers, synthetic (liposomes, solid nanoparticles, nanoemulsions, nanostructured carriers, niosomes, proniosomes, cubosomes) cell-derived ones (extracellular vesicles cell membrane-derived nanocarriers), considered one successful systems due reasonable biocompatibility ability cross BBB. This review aims provide complete up-to-date view on varied whether FDA-approved, involved clinical trials, used vitro vivo studies, for inflammatory, cancerous, infectious diseases.

Language: Английский

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Cavitation Feedback Control of Focused Ultrasound Blood-Brain Barrier Opening for Drug Delivery in Patients with Parkinson’s Disease

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2607 - 2607

Published: Nov. 26, 2022

Magnetic resonance-guided focused ultrasound (MRgFUS), in conjunction with circulating microbubbles, is an emerging technology that can transiently enhance the permeability of blood-brain barrier (BBB) locally and non-invasively to facilitate targeted drug delivery brain. In this clinical trial, feasibility safety BBB modulation putamen were evaluated for biweekly therapeutic agent patients Parkinson's disease. The performance MRgFUS system's cavitation feedback controller active power throughout exposures was examined. unilaterally by ExAblate Neuro system operating at 220 kHz. Definity microbubbles infused via a saline bag gravity drip rate 4 µL/kg per 5 min. A emissions-based employed modulate acoustic automatically according prescribed target dose levels. opening measured Gadolinium (Gd)-enhanced T1-weighted MR imaging, presence potential micro-hemorrhages induced assessed T2*-weighted imaging. total 12 treatment sessions carried out across four patients, levels ranging from 0.20-0.40. elevated successfully all treatments, 14% ± 6% mean increase Gd-enhanced MRI signal intensity relative untreated contralateral side. No indications red blood cell extravasations observed on imaging scans acquired one day following each session. effective modulating ensure enhancement while avoiding micro-hemorrhages, however, further technical advancements are warranted improve its use wide variety brain diseases.

Language: Английский

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The blood-brain barrier, a key bridge to treat neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102070 - 102070

Published: Sept. 11, 2023

Language: Английский

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The road ahead to successful BBB opening and drug-delivery with focused ultrasound

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 901 - 913

Published: July 15, 2024

Language: Английский

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A review of temporal interference, nanoparticles, ultrasound, gene therapy, and designer receptors for Parkinson disease

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 23, 2024

In this review, we summarize preclinical and clinical trials investigating innovative neuromodulatory approaches for Parkinson disease (PD) motor symptom management. We highlight the following technologies: temporal interference, nanoparticles drug delivery, blood-brain barrier opening, gene therapy, optogenetics, upconversion nanoparticles, magnetothermal magnetoelectric ultrasound-responsive designer receptors exclusively activated by drugs. These studies establish basis novel promising treatments PD symptoms.

Language: Английский

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Molecular heterogeneity in the substantia nigra: A roadmap for understanding PD motor pathophysiology

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 175, P. 105925 - 105925

Published: Nov. 11, 2022

As the ability to capture single-cell expression profiles has grown in recent years, neuroscientists studying a wide gamut of brain regions have discovered remarkable heterogeneity within seemingly related populations (Saunders et al., 2018a; Zeisel 2015). These "molecular subtypes" been demonstrated even nuclei expressing same neurotransmitter Poulin 2020; Ren 2019; Okaty 2020). Recently, dopamine (DA) neurons substantia nigra pars compacta (SNc) and adjacent ventral tegmental area (VTA) revealed be diverse not only when comparing between these two dopaminergic nuclei, but them, with distribution identified subtypes often agnostic traditional neuroanatomical boundaries Hook 2018; Kramer La Manno 2016; 2014; Tiklova 2018). Such molecularly defined subpopulations subject several studies. Investigations ultimately unveiled many distinctive properties across domains, such as their axonal projections functional (Poulin Wu Pereira Luppi 2021; Evans 2017; key differences begun corroborate biological relevance DA neuron taxonomic schemes. We hypothesize that putative molecular subtypes, circuits, could shed light on variety dopamine-related symptoms observed diseases including depression, chronic pain, addiction, Parkinson's Disease. While it is difficult reconcile how single can involved so unrelated phenotypes, one solution existence individual pathways serving different functions, distinct nodes for pathways. Indeed, this conceptual framework already dogma anatomically pathways, mesocortical, mesolimbic mesostriatal (Bjorklund & Dunnett, 2007). Here, we discuss our existing knowledge attempt provide roadmap novel insights into motor disease (PD) (Fig. 1A). By exploring correlating relative degeneration SNc, may gain deeper understanding cell-intrinsic mechanisms underlying why some degenerate more than others PD. Similarly, by mapping inputs, projections, functions better understand roles circuit-level dysfunction diseases.

Language: Английский

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Focused ultrasound therapy: Back to the future

Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 121, P. 106023 - 106023

Published: Feb. 2, 2024

•MRgFUS is an FDA approved, incisionless, therapy for the treatment of ET and PD.•RCTs MRgFUS targeting VIM, GPi STN demonstrate benefit.•Case series PTT also suggest significant benefit.•Low-intensity can transiently open BBB.•Future technical developments studies will further define role MRgFUS. The surgical movement disorders, primarily tremor, started with radiofrequency lesioning globus pallidus thalamus in 1950s [[1]Hassler R. Riechert T. Symptomatology & surgery extrapyramidal disorders.Med. Klin. 1958; 53: 817-824http://www.ncbi.nlm.nih.gov/pubmed/13551836PubMed Google Scholar]. While this became a state-of-the-art over following decades, bilateral lesions were associated side effects such as gait, balance, speech disturbances [[2]Krayenbühl H. Wyss O.A.M. Yasargil M.G. Bilateral thalamotomy pallidotomy parkinsonism.J. Neurosurg. 1961; 18: 429-444https://doi.org/10.3171/jns.1961.18.4.0429Crossref PubMed Scopus (61) In 70's, radiosurgery gamma knife showed promise because procedure was incisionless. However, it used ionizing radiation, target could not be confirmed real-time, effect delayed by around six months. Consequently, never mainstream [[3]Walter B.L. Vitek J.L. Surgical Parkinson's disease.Lancet Neurol. 2004; 3: 719-728https://doi.org/10.1016/S1474-4422(04)00934-2Abstract Full Text PDF (138) Then, 1997, approved deep brain stimulation (DBS) tremor which gold standard treatment, no lesion made, reversible adjustable, allowed intraoperative confirmation target, and, done bilaterally 2016, we went 'back to future' when Magnetic Resonance-guided Focused Ultrasound (MRgFUS) ablation novel, tool make disorders (Fig. 1). Since its appearance early 2000s, technology has progressively gained traction disorder community incisionless therapy. consists helmet-shaped phased array transducer 1024 elements, controlled individually refocus ultrasound beams common focal point. Guided real-time magnetic resonance imaging, pass through intact skull focus precisely onto selected targets, major advantage avoiding penetration tissue between target. When focused at high frequency (MRgHiFU) (650 kHz) continuous-wave mode, cumulative thermal dose point (target) great enough produce coagulative necrosis. During MRgHiFU procedures, verified real time MR-thermography map, clinical feedback, structural MRI. addition, initial delivery low-energy sonication allows 'test lesion' only after exam shows benefit without effects, energy (temperature) increased becomes permanent, immediate results evident [[4]Krishna V. Sammartino F. Rezai A. A review current therapies, challenges, future directions transcranial technology: advances diagnosis treatment.JAMA 2017; : 1-9https://doi.org/10.1001/jamaneurol.2017.3129Crossref (171) Scholar] 2). Conceptually, any that been treated or DBS from lesioning. there ample evidence (ventral intermediate nucleus, VIM) [[5]Elias W.J. Lipsman N. Ondo W.G. Ghanouni P. Kim Y.G. Lee W. Schwartz M. Hynynen K. Lozano A.M. Shah B.B. Huss D. Dallapiazza R.F. Gwinn Witt J. Ro S. Eisenberg H.M. Fishman P.S. Gandhi Halpern C.H. Chuang Butts Pauly Tierney T.S. Hayes M.T. Cosgrove G.R. Yamaguchi Abe Taira Chang J.W. randomized trial essential tremor.N. Engl. Med. 2016; 375: 730-739https://doi.org/10.1056/NEJMoa1600159Crossref (687) Scholar,[6]Bond A.E. D.S. Warren Harrison M.B. Sperling S.A. Wang X.-Q. Elias Safety efficacy patients medication-refractory, tremor-dominant Parkinson disease.JAMA 74: 1412https://doi.org/10.1001/jamaneurol.2017.3098Crossref (210) Scholar], pars interna (GPi) [[7]Krishna Kaplitt Baltuch G. W.-C. Martinez Fernandez del Alamo Eleopra Guridi Khemani McDannold Fasano Constantinescu Schlesinger I. Dalvi Trial disease.N. 2023; 388: 683-693https://doi.org/10.1056/NEJMoa2202721Crossref (19) subthalamic nucleus (STN) [[8]Martínez-Fernández Máñez-Miró J.U. Rodríguez-Rojas Álamo Hernández-Fernández Pineda-Pardo J.A. Monje M.H.G. Fernández-Rodríguez B. Mata-Marín Guida Alonso-Frech Obeso Gasca-Salas C. Vela-Desojo L. Randomized subthalamotomy 2020; 383: 2501-2513https://doi.org/10.1056/NEJMoa2016311Crossref (99) other structures pallido-thalamic tract (PTT) [[9]Gallay M.N. Moser Rossi Magara Strasser Bühler Kowalski Pourtehrani Dragalina Federau Jeanmonod pallidothalamic tractotomy chronic therapy-resistant disease 51 consecutive patients: single center experience.Front. Surg. 6https://doi.org/10.3389/fsurg.2019.00076Crossref (34) cerebello-thalamic (CTT) [[10]Gallay accuracy MR-guided functional neurosurgery: single-center experience 253 targets 180 treatments.J. 2018; https://doi.org/10.3171/2017.12.jns172054Crossref considered but require assessment. If, on hand, low (MRgLiFU) (220 pulsed manner, low, due physical, non-thermal, interactions. This "per se" induce neuromodulation intravenous administration bubble-rich contrast agent. convergence bubbles circulation being leveraged preclinical attempts BBB, temporarily 'loosening' tight junctions endothelial cells normally restrict drugs endovascular space into surrounding tissue. Here aim summarize data regarding a) indications Essential (ET) (PD); b) investigational PD; 3) investigations MRgLiFU. first two open-label unilateral FUS-VIM medically refractory published 2013 [[11]Elias Voss Loomba Khaled Zadicario E. Frysinger R.C. Wylie Monteith S.J. Druzgal Wintermark pilot study 2013; 369: 640-648https://doi.org/10.1056/nejmoa1300962Crossref (0) Scholar,[12]Lipsman M.L. Huang Y. Sankar Chapman tremor: proof-of-concept study.Lancet https://doi.org/10.1016/S1474-4422(13)70048-6Abstract (438) suggested might effective treat improvements both disability quality life. Soon after, colleagues pivotal follow-up analyses 3 [[13]Halpern Santini Aldrich Jung N.Y. Rosenberg Three-year prospective tremor.Neurology. 2019; 93https://doi.org/10.1212/WNL.0000000000008561Crossref (62) 5 years [[14]Cosgrove V.E. imaging–guided 5-year results.J. 2022; 1-6https://doi.org/10.3171/2022.6.JNS212483Crossref (8) Using Clinical Rating Scale Tremor (CRST), they found contralateral postural maintained > 70 % improvement years. combined scores postural, kinetic rest well writing, drawing spirals pouring cup (CRST + B) affected hand improved 55 one year, 40 score (CRST-C) decreased 67 45 As far are concerned, reported analysis adverse events (AEs) including above [[15]Fishman Krishna Yamada Igase Kashima Neurological event profile tremor.Mov. Disord. 33: 843-847https://doi.org/10.1002/mds.27401Crossref (79) They documented 443 AEs 186 grouped them three categories: 1. Frame related, pin site numbness, infection, pain; 2. Sonication headache, scalp burn, lightheadedness, nausea, vomiting; 3. Thalamotomy divided four subgroups: A) Sensory disturbances, paresthesia, dysesthesias, dysgeusia; Speech swallowing dysarthria, dysphagia; C) Balance gait ataxia; D) Weakness limb coordination. Most mild (79 %) moderate (20 %). Of 1 (n = 5) rated severe, sonication-related transient, lasting less than days post-procedure. changes most neurological (45 all AEs), none severe 91 (84 92) mild. Severe rare (3 balance deficits) December 2022. (NCT04112381) still published, previous smaller [16Iorio‐Morin Yamamoto Sarica Zemmar Levesque Brisebois Germann Loh Boutet G.J.B. Azevedo Adam Patel U. Lenis Kalia S.K. Hodaie (BEST‐FUS Phase 2 trial).Mov. 2021; 36: 2653-2662https://doi.org/10.1002/mds.28716Crossref (45) Scholar, 17Martínez-Fernández Mahendran Imbach L.L. Büchele Rodriguez-Rojas Werner Matarazzo Gonzalez-Quarante L.H. Deuschl Stieglitz Baumann C.R. staged resonance-guided case study.J. Psychiatry. 92: 927-931https://doi.org/10.1136/jnnp-2020-325278Crossref (26) 18Fukutome Hirabayashi Osakada Kuga Ohnishi imaging-guided tremor.Stereotact. Funct. 100: 44-52https://doi.org/10.1159/000518662Crossref (14) support relative safety FUS-VIM. BEST-FUS trial, 10 received second, contralateral, 9 months [[16]Iorio‐Morin primary outcome life response question; 'given what you know now, would second again', outcomes met. Improvement severity expected, more importantly, benign. After had some difficulties resolved within number missteps during 6 m tandem walking slightly up initially returned baseline There person dysarthria persisted 3-month On Spanish-Swiss study, where secondary outcome, underwent least [[17]Martínez-Fernández Six experienced instability weeks, permanent. concerned 71 total CRST (67 B, 81 C). 66 head voice respectively PD, thalamic VIM (TDPD), advanced disease. These nuclei have ablative procedures PD motor complications (MRCs), respectively, decades. explored, PTT. summary main trials each Table European Union, additional application.Table 1Main disease.ReferenceStudy designTargetNumber patientsFollow-upAdverse last (12 months)Primary outcomeBond et al., 2017 [[6]Bond Scholar]Prospective, randomized, sham-controlled, double blind trialThalamic Vim27 TDPD patients. 20 receiving 7 sham procedure3 blinded (1ary outcome), 12 labelHemiparesis n (10 Paresthesia (25 %)Ataxia (5 %)Vocal change %)62 median reduction subscores (parts on-medication active-treatment arm vs 22 sham-procedure armMartínez-Fernández 2020 double-blind trialSTN40 asymmetrical 27 13 procedure4 labelLevodopa-induced dyskinesia (7 %)Clumsy %)Dysarthria (4 %)Balance %)−53 mean MDS-UPDRS III off-medication 4.2 arm.-Between-group difference 8.1 points.Krishna 2023 trialGPi94 69 25 labelDysarthria (2 %)15 Serious 10)−69 responders rate* 32 arm.Mean MDS---UPDRS 6.0 points.-Mean IV 5.1 pointsGallay Scholar]Open-label seriesPTT47 (15 treatment)12 %)−51 off-medication.-Mean 84 rigidity, 73 bradykinesia hemibody.−100 levodopa-induced dyskinesiasAE: events; CRST: Tremor; GPi: interna; MDS-UPDRS: Movement Disorders Society-Unified Disease Scale; PD: disease; PTT: tract. STN: nucleus; TDPD: dominant VIM: ventral nucleus. Open table new tab AE: earliest placebo. Primary groups. ON-medication 62 year. quite persistent months: finger paresthesia (1), orofacial (4), ataxia hemiparesis (2), (1). authors commented encouraging, dealing learning curve, likely improve "as monitoring improves" (Table 26 TDPD, Israel long term results, relief few [[19]Sinai Nassar Sprecher Zaaroor disease: long-term Parkinsons Dis. 12: 199-206https://doi.org/10.3233/JPD-212810Crossref (23) Median hemi-CRST hemi-UPDRS month (N 26) 60 92 %, 53 61 7). permanent transient unsteadiness, ataxia, weakness, taste changes, then resolved. complete, 8 partial return. Similar Japan [[20]Yamamoto Ito Fukutake Odo Kamei YamaguchiI 1-year study.Neurol. Med.-Chir. (oa.2020-0370)https://doi.org/10.2176/nmc.oa.2020-0370Crossref (17) recently (2021) GPi, indicated MRCs. An label 20) FUS-GPi OFF-medication MDS-UPDRS-III 43 Unified Dyskinesia (UDysRS). No AE occurred frequent complication [[21]Eisenberg C.E. feasibility.J. 135: 792-798https://doi.org/10.3171/2020.6.JNS192773Crossref (28) subsequent double-blind, (3:1 ratio), sham-controlled enrolled 94 MRCs positive response, defined (improvement) points either part state OR UDysRS state, clinically meaningful worsening scale, percentage twice group (69 compared (33 active 65) 29 met criterion only, 28 criteria, 31 neither criterion. 22), these numbers 0 68 respectively. For side, 21 MDS-UPDRS-IV 48 %. Corresponding 39 who months, 30 continued included 1), visual disturbance 1) facial weakness At patient remained Anecdotally, successful presenting disabling dyskinesias [[22]Stieglitz Oertel M.F. Parkinson‐related dyskinesia—a report.Mov. Clin. Pract. 9: 647-651https://doi.org/10.1002/mdc3.13462Crossref (2) Contrary classically therapeutic neurosurgical [[23]Máñez-Miró Del Martínez-Fernández Present management systematic review.Expert Rev. Neurother. 21: 533-545https://doi.org/10.1080/14737175.2021.1911649Crossref concepts changed late 80s parkinsonian circuitry elucidated [24Aziz T.Z. Peggs Sambrook M.A. Crossman A.R. Lesion alleviation 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism primate.Mov. 1991; 6: 288-292https://doi.org/10.1002/mds.870060404Crossref (442) 25Bergman Wichmann DeLong M.R. Reversal experimental nucleus.Science. 1990; 80–https://doi.org/10.1126/science.2402638Crossref 26Guridi Herrero Luquin Guillén Rube

Language: Английский

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