Journal Description
Neurology International
Neurology International
is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of neurology and neuroscience, published bimonthly online by MDPI (from Volume 12 issue 3 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, Embase, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 23.3 days after submission; acceptance to publication is undertaken in 3.9 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Impact Factor:
3.0 (2022);
5-Year Impact Factor:
2.2 (2022)
Latest Articles
Outcome after Intracerebral Haemorrhage and Decompressive Craniectomy in Older Adults
Neurol. Int. 2024, 16(3), 590-604; https://doi.org/10.3390/neurolint16030044 - 20 May 2024
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Objective: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy
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Objective: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). Methods: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV–V) and unfavourable outcome (GOS I to III). Results: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). Conclusion: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.
Full article
Open AccessReview
The Effectiveness of Paired Associative Stimulation on Motor Recovery after Stroke: A Scoping Review
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Andrea Baroni, Annibale Antonioni, Giulia Fregna, Nicola Lamberti, Fabio Manfredini, Giacomo Koch, Alessandro D’Ausilio and Sofia Straudi
Neurol. Int. 2024, 16(3), 567-589; https://doi.org/10.3390/neurolint16030043 - 14 May 2024
Abstract
Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural
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Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.
Full article
(This article belongs to the Special Issue Treatment Strategy and Mechanism of Acute Ischemic Stroke)
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Open AccessCase Report
Supranuclear Palsy as an Initial Presentation of the Adult-Onset Niemann-Pick Type C
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Ali A. Mohamed, Willy Gan, Denis Babici, Veronica Hagan, Raphael Wald and Marc Swerdloff
Neurol. Int. 2024, 16(3), 561-566; https://doi.org/10.3390/neurolint16030042 - 13 May 2024
Abstract
(1) Background: Niemann–Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal–lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The
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(1) Background: Niemann–Pick type C1 (NP-C1) is a lysosomal storage disorder that results in the defective trafficking of cholesterol and other cellular lipids in the endosomal–lysosomal pathway. This rare autosomal recessive disorder presents in three forms based on the age of onset. The adult form presents in patients greater than 15 years of age but is rarely seen after the age of 30. Common symptoms of the late adult-onset category of NP-C1 include progressive cognitive impairment and ataxia, with psychiatric and movement disorders presenting less frequently than in other forms of NP-C1. Dystonic movement disorders present most frequently, along with chorea, myoclonus, and parkinsonism. Herein, we present a rare case of NP-C1, diagnosed at age 35 with an initial symptom of supranuclear palsy. The goal of the presented case is to highlight the importance of the neurological examination and an inclusive differential diagnosis in patients with new-onset supranuclear palsy. (2) Methods: A single case report. (3) Results: A 46-year-old male with a past medical history of NP-C1 was admitted to the hospital for respiratory distress. He was noted to have a supranuclear gaze palsy with partially preserved voluntary saccades to the right. His mother revealed that he first had difficulty moving his eyes at the age of 34. After multiple consultations and genetic testing one year later, he was diagnosed with NP-C1. (4) Conclusions: Because NP-C1 affects many regions of the brain responsible for eye movements, neurological eye assessments can be a useful tool in diagnoses. Furthermore, eye movement abnormalities may be the initial presenting symptom of NP-C1, predisposing patients to misdiagnosis with progressive supranuclear palsy and other conditions that may mimic early-stage NP-C1. Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past. The NP-C Suspicion Index was developed to assist in diagnoses, but its efficacy is unclear with late adult-onset NP-C1. Although no cure exists, early identification can facilitate an improved symptom management course for patients. Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1. Delays between symptom onset and treatment initiation are likely to result in poorer outcomes and a progression of neurological symptoms. High doses may present tolerance concerns, especially in cases of delayed treatment and advanced neurological deficit.
Full article
(This article belongs to the Collection Advances in Neurodegenerative Diseases)
Open AccessArticle
The Usefulness of Factor XIII Concentration Assessment in Patients in the Acute Phase of Ischaemic Stroke Treated with Thrombolysis
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Małgorzata Wiszniewska, Urszula Włodarczyk, Magdalena Sury, Artur Słomka, Natalia Piekuś-Słomka, Anna Żdanowicz and Ewa Żekanowska
Neurol. Int. 2024, 16(3), 551-560; https://doi.org/10.3390/neurolint16030041 - 10 May 2024
Abstract
Background and Aims: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study’s main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with
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Background and Aims: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study’s main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). Methods: The study was conducted in two groups of 84 patients with AIS: group I—with thrombolytic therapy and group II—without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients’ activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil–lymphocyte ratio (NLR index), and the concentration of factor XIII-A. Results: In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. Conclusions: In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.
Full article
(This article belongs to the Special Issue Treatment Strategy and Mechanism of Acute Ischemic Stroke)
Open AccessArticle
Dynamics in Redox-Active Molecules Following Ischemic Preconditioning in the Brain
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Terezia Lysikova, Anna Tomascova, Maria Kovalska, Jan Lehotsky, Katarina Leskova Majdova, Peter Kaplan and Zuzana Tatarkova
Neurol. Int. 2024, 16(3), 533-550; https://doi.org/10.3390/neurolint16030040 - 9 May 2024
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It is well known that the brain is quite vulnerable to oxidative stress, initiating neuronal loss after ischemia-reperfusion (IR) injury. A potent protective mechanism is ischemic preconditioning (IPC), where proteins are among the primary targets. This study explores redox-active proteins’ role in preserving
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It is well known that the brain is quite vulnerable to oxidative stress, initiating neuronal loss after ischemia-reperfusion (IR) injury. A potent protective mechanism is ischemic preconditioning (IPC), where proteins are among the primary targets. This study explores redox-active proteins’ role in preserving energy supply. Adult rats were divided into the control, IR, and IPC groups. Protein profiling was conducted to identify modified proteins and then verified through activity assays, immunoblot, and immunohistochemical analyses. IPC protected cortex mitochondria, as evidenced by a 2.26-fold increase in superoxide dismutase (SOD) activity. Additionally, stable core subunits of respiratory chain complexes ensured sufficient energy production, supported by a 16.6% increase in ATP synthase activity. In hippocampal cells, IPC led to the downregulation of energy-related dehydrogenases, while a significantly higher level of peroxiredoxin 6 (PRX6) was observed. Notably, IPC significantly enhanced glutathione reductase activity to provide sufficient glutathione to maintain PRX6 function. Astrocytes may mobilize PRX6 to protect neurons during initial ischemic events, by decreased PRX6 positivity in astrocytes, accompanied by an increase in neurons following both IR injury and IPC. Maintained redox signaling via astrocyte-neuron communication triggers IPC’s protective state. The partnership among PRX6, SOD, and glutathione reductase appears essential in safeguarding and stabilizing the hippocampus.
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Open AccessReview
Obstructive Sleep Apnea in Pregnancy: A Comprehensive Review of Maternal and Fetal Implications
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Antonino Maniaci, Luigi La Via, Basilio Pecorino, Benito Chiofalo, Giuseppe Scibilia, Salvatore Lavalle and Paolo Scollo
Neurol. Int. 2024, 16(3), 522-532; https://doi.org/10.3390/neurolint16030039 - 7 May 2024
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Obstructive sleep apnea (OSA) is a prevalent yet underdiagnosed condition in pregnancy, associated with various maternal and fetal complications. This review synthesizes the current evidence on the epidemiology, pathophysiology, and neurological consequences of OSA in pregnancy, along with the potential management strategies. Articles
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Obstructive sleep apnea (OSA) is a prevalent yet underdiagnosed condition in pregnancy, associated with various maternal and fetal complications. This review synthesizes the current evidence on the epidemiology, pathophysiology, and neurological consequences of OSA in pregnancy, along with the potential management strategies. Articles were sourced from the PubMed, EMBASE, and Cochrane databases until 2023. Our comprehensive review highlights that the incidence of OSA increases during pregnancy due to physiological changes such as weight gain and hormonal fluctuations. OSA in pregnancy is linked with gestational hypertension, pre-eclampsia, gestational diabetes, and potential adverse fetal outcomes such as intrauterine growth restriction and preterm birth. Continuous positive airway pressure (CPAP) therapy remains the most effective management strategy for pregnant women with OSA. However, adherence to CPAP therapy is often suboptimal. This comprehensive review underscores the importance of the early recognition, timely diagnosis, and effective management of OSA in pregnancy to improve both maternal and fetal outcomes. Future research should focus on enhancing screening strategies and improving adherence to CPAP therapy in this population.
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Open AccessCorrection
Correction: Szymanowicz et al. Headache and NOTCH3 Gene Variants in Patients with CADASIL. Neurol. Int. 2023, 15, 1238–1252
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Oliwia Szymanowicz, Izabela Korczowska-Łącka, Bartosz Słowikowski, Małgorzata Wiszniewska, Ada Piotrowska, Ulyana Goutor, Paweł P. Jagodziński, Wojciech Kozubski and Jolanta Dorszewska
Neurol. Int. 2024, 16(3), 518-521; https://doi.org/10.3390/neurolint16030038 - 6 May 2024
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Full article
(This article belongs to the Special Issue Migraines and Beyond: Advances in the Pathogenesis and Treatment of Chronic Headache Disorders)
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Open AccessReview
Oxidative Stress and Neurodegeneration: Insights and Therapeutic Strategies for Parkinson’s Disease
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Erjola Bej, Patrizia Cesare, Anna Rita Volpe, Michele d’Angelo and Vanessa Castelli
Neurol. Int. 2024, 16(3), 502-517; https://doi.org/10.3390/neurolint16030037 - 29 Apr 2024
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative condition marked by the gradual deterioration of dopaminergic neurons in the substantia nigra. Oxidative stress has been identified as a key player in the development of PD in recent studies. In the first part, we
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Parkinson’s disease (PD) is a progressive neurodegenerative condition marked by the gradual deterioration of dopaminergic neurons in the substantia nigra. Oxidative stress has been identified as a key player in the development of PD in recent studies. In the first part, we discuss the sources of oxidative stress in PD, including mitochondrial dysfunction, dopamine metabolism, and neuroinflammation. This paper delves into the possibility of mitigating oxidative stress as a potential treatment approach for PD. In addition, we examine the hurdles and potential of antioxidant therapy, including the challenge of delivering antioxidants to the brain and the requirement for biomarkers to track oxidative stress in PD patients. However, even if antioxidant therapy holds promise, further investigation is needed to determine its efficacy and safety in PD treatment.
Full article
(This article belongs to the Collection Advances in Neurodegenerative Diseases)
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Open AccessReview
Pain Catastrophizing: How Far Have We Come
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Katarina Simic, Boris Savic and Nebojsa Nick Knezevic
Neurol. Int. 2024, 16(3), 483-501; https://doi.org/10.3390/neurolint16030036 - 26 Apr 2024
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The perception of pain is strongly influenced by various social, emotional, and cognitive factors. A psychological variable which has consistently been shown to exert its influence on pain is a cognitive process referred to as pain catastrophizing. Numerous studies have found it to
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The perception of pain is strongly influenced by various social, emotional, and cognitive factors. A psychological variable which has consistently been shown to exert its influence on pain is a cognitive process referred to as pain catastrophizing. Numerous studies have found it to be a strong predictor of pain intensity and disability across different clinical populations. It signifies a maladaptive response to pain marked by an exaggerated negative assessment, magnification of symptoms related to pain, and, in general, a tendency to experience marked pain-related worry, as well as experiencing feelings of helplessness when it comes to dealing with pain. Pain catastrophizing has been correlated to many adverse pain-related outcomes, including poor treatment response, unsatisfactory quality of life, and high disability related to both acute and chronic pain. Furthermore, there has been consistent evidence in support of a correlation between pain catastrophizing and mental health disorders, such as anxiety and depression. In this review, we aim to provide a comprehensive overview of the current state of knowledge regarding pain catastrophizing, with special emphasis on its clinical significance, and emerging treatment modalities which target it.
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Open AccessArticle
An Extensive Study Regarding the Microscopic Anatomy of the Early Fetal Human Optic Nerve
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Mihai Alin Publik, Florin Mihail Filipoiu, Adrian Vasile Dumitru, Andrei Precup, Ioan-Andrei Petrescu, Iulian Slavu, Raluca Florentina Tulin, Adrian Tulin, Andra Ioana Baloiu, Monica Mihaela Cirstoiu and Octavian Munteanu
Neurol. Int. 2024, 16(3), 470-482; https://doi.org/10.3390/neurolint16030035 - 24 Apr 2024
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The development of the optic nerve and its surrounding tissues during the early fetal period is a convoluted period because it spans both the organogenesis period and the fetal period. This study details the microscopic anatomy and histoembryology of the optic nerve in
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The development of the optic nerve and its surrounding tissues during the early fetal period is a convoluted period because it spans both the organogenesis period and the fetal period. This study details the microscopic anatomy and histoembryology of the optic nerve in embryos during the early fetal period, including the second half of the first trimester of pregnancy. Serial sections through the orbit of variously aged embryos allowed us to analyze the nerve in both longitudinal and transverse aspects. A histological assessment and description of the structures surrounding and inside the nerve were performed, highlighting the cellular subtypes involved. By employing immunohistochemical techniques, we could characterize the presence and distribution of astrocytes within the optic nerve. Our findings suggest that by the 8th gestational week (WG) the structures are homologs to all the adult ones but with an early appearance so that maturation processes take place afterward. By this age, the axons forming the nerve are definitive adult axons. The glial cells do not yet exhibit adult phenotype, but their aspect becomes adult toward the 13th week. During its development the optic nerve increases in size then, at 14 weeks, it shrinks considerably, possibly through its neural maturation process. The morphological primordium of the blood–nerve barrier can be first noted at 10 WG and at 13 WG the morphological blood–nerve barrier is definitive. The meningeal primordium can be first noted as a layer of agglomerated fibroblasts, later toward 13 WG splitting in pachymeninx and leptomeninges and leaving space for intrinsic blood vessels.
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Open AccessArticle
The Impact of Acute Postoperative Pain in Developing Chronic Pain after Total Knee Arthroplasty
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Nebojsa Nick Knezevic, Osman Syed, Christopher Kabir, Aisha Patel, Isabel Rao Shuai and Antony R. Tharian
Neurol. Int. 2024, 16(2), 459-469; https://doi.org/10.3390/neurolint16020034 - 18 Apr 2024
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While total knee arthroplasties (TKAs) are performed with the intent to reduce pain, chronic postsurgical pain (CPSP) is one of the most well-documented complications that can occur following surgery. This study aimed to assess whether perioperative factors, focusing on acute postsurgical pain and
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While total knee arthroplasties (TKAs) are performed with the intent to reduce pain, chronic postsurgical pain (CPSP) is one of the most well-documented complications that can occur following surgery. This study aimed to assess whether perioperative factors, focusing on acute postsurgical pain and perioperative opioid consumption, were associated with the development of chronic postsurgical pain. Under general anesthesia, 108 patients underwent TKA and were treated postoperatively with a multimodal analgesia approach. Numeric Rating Scale (NRS) pain scores at rest and with movement were recorded on postoperative days 0–3, 7, 14, and 30. Patients were sent a survey to assess chronic pain at months 22–66, which was examined as a single-group post hoc analysis. Based on the responses, patients were either classified into the CPSP or non-CPSP patient group. Chronic postsurgical pain was defined as an NRS score ≥ 4 with movement and the presence of resting pain. The primary outcome was a change in NRS. There were no differences in NRS pain scores with movement in the first 30 days postoperatively between patients with CPSP and without CPSP. Each unit increase in resting pain on postoperative days 3 and 14 was associated with significantly greater odds of CPSP presence (OR = 1.52; OR = 1.61, respectively), with a trend towards greater odds of CPSP at days 7 and 30 (OR = 1.33; OR = 1.43, respectively). We found that very intense pain in the initial phase seems to be related to the development of CPSP after TKA.
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Open AccessBrief Report
Thecaloscopy Reduces the Risk of Recurrent Perineural (Tarlov) Cysts after Microsurgical Resection
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Michael Luchtmann, Angelika Klammer, Mircea-Alin Iova, André Roth, Vijay Kumar Chanamolu, Christian Mawrin and Jan-Peter Warnke
Neurol. Int. 2024, 16(2), 450-458; https://doi.org/10.3390/neurolint16020033 - 17 Apr 2024
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Sacral Tarlov cysts (TCs), often asymptomatic, can cause significant pain and severe neurological dysfunction. Conventional treatments are generally associated with high recurrence and complication rates. Specifically, the substantial recurrence rates, which can reach as high as 50%, significantly impact long-term outcomes. Recent evidence
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Sacral Tarlov cysts (TCs), often asymptomatic, can cause significant pain and severe neurological dysfunction. Conventional treatments are generally associated with high recurrence and complication rates. Specifically, the substantial recurrence rates, which can reach as high as 50%, significantly impact long-term outcomes. Recent evidence increasingly supports the hypothesis that the formation of Tarlov cysts (TCs) may be associated with inflammatory processes within the nerve root sheath, further exacerbated by elevated cerebrospinal fluid (CSF) pressure. This retrospective study explores thecaloscopy, combined with surgical techniques, as a more effective alternative. We observed a total of 78 patients, 48 of whom underwent endoscopic fenestration of the arachnoid sheath in addition to microsurgical resection of the TC. We found that the fenestration of the arachnoid sheath at the level of lumbosacral spinal nerve root entry led to a significantly decreased risk of developing recurrent TCs (5/48 vs. 9/30). Only one of the patients suffered from a persistent new bladder dysfunction after microsurgical resection. This presented technique provides a promising treatment path for the future management of TCs, offering a safe and more effective treatment option compared to previous methods. Additionally, the advantages of the thecaloscopy provide pathophysiological implications regarding the development of perineural cysts.
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Open AccessReview
Neurocognitive Impairment and Social Cognition in Parkinson’s Disease Patients
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Triantafyllos Doskas, Konstantinos Vadikolias, Konstantinos Ntoskas, George D. Vavougios, Dimitrios Tsiptsios, Polyxeni Stamati, Ioannis Liampas, Vasileios Siokas, Lambros Messinis, Grigorios Nasios and Efthimios Dardiotis
Neurol. Int. 2024, 16(2), 432-449; https://doi.org/10.3390/neurolint16020032 - 16 Apr 2024
Abstract
In addition to motor symptoms, neurocognitive impairment (NCI) affects patients with prodromal Parkinson’s disease (PD). NCI in PD ranges from subjective cognitive complaints to dementia. The purpose of this review is to present the available evidence of NCI in PD and highlight the
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In addition to motor symptoms, neurocognitive impairment (NCI) affects patients with prodromal Parkinson’s disease (PD). NCI in PD ranges from subjective cognitive complaints to dementia. The purpose of this review is to present the available evidence of NCI in PD and highlight the heterogeneity of NCI phenotypes as well as the range of factors that contribute to NCI onset and progression. A review of publications related to NCI in PD up to March 2023 was performed using PubMed/Medline. There is an interconnection between the neurocognitive and motor symptoms of the disease, suggesting a common underlying pathophysiology as well as an interconnection between NCI and non-motor symptoms, such as mood disorders, which may contribute to confounding NCI. Motor and non-motor symptom evaluation could be used prognostically for NCI onset and progression in combination with imaging, laboratory, and genetic data. Additionally, the implications of NCI on the social cognition of afflicted patients warrant its prompt management. The etiology of NCI onset and its progression in PD is multifactorial and its effects are equally grave as the motor effects. This review highlights the importance of the prompt identification of subjective cognitive complaints in PD patients and NCI management.
Full article
(This article belongs to the Special Issue Exclusive Papers from the Editorial Board Members (EBMs) and Invited Scholars of Neurology International)
Open AccessArticle
[125I]IPC-Lecanemab: Synthesis and Evaluation of Aβ-Plaque-Binding Antibody and Comparison with Small-Molecule [18F]Flotaza and [125I]IBETA in Postmortem Human Alzheimer’s Disease
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Christopher Liang, Cayz G. Paclibar, Noresa L. Gonzaga, Stephanie A. Sison, Harman S. Bath, Agnes P. Biju and Jogeshwar Mukherjee
Neurol. Int. 2024, 16(2), 419-431; https://doi.org/10.3390/neurolint16020031 - 8 Apr 2024
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Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging
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Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging a therapeutic antibody, Lecanemab, in a postmortem AD brain anterior cingulate. [125I]5-iodo-3-pyridinecarboxamido-Lecanemab ([125I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([125I]iodo)-3-pyridinecarboxylate with Lecanemab in modest yields. The distinct binding of [125I]IPC-Lecanemab to Aβ-rich regions in postmortem human AD brains was higher in grey matter (GM) containing Aβ plaques compared to white matter (WM) (GM/WM was 1.6). Anti-Aβ immunostaining was correlated with [125I]IPC-Lecanemab regional binding in the postmortem AD human brains. [125I]IPC-Lecanemab binding was consistent with the binding of Aβ small molecules, [18F]flotaza and [125I]IBETA, in the same subjects. [18F]Flotaza and [125I]IBETA, however, exhibited significantly higher GM/WM ratios (>20) compared to [125I]IPC-Lecanemab. Our results suggest that radiolabeled [125I]IPC-Lecanemab retains the ability to bind to Aβ in human AD and may therefore be useful as a PET imaging radiotracer when labeled as [124I]IPC-Lecanemab. The ability to directly visualize in vivo a promising therapeutic antibody for AD may be useful in treatment planning and dosing and could be complimentary to small-molecule diagnostic imaging to assess outcomes of therapeutic interventions.
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Open AccessReview
Mortality Predictors for Adult Patients with Mild-to-Moderate Traumatic Brain Injury: A Literature Review
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Ansam Eghzawi, Alameen Alsabbah, Shatha Gharaibeh, Iktimal Alwan, Abeer Gharaibeh and Anita V. Goyal
Neurol. Int. 2024, 16(2), 406-418; https://doi.org/10.3390/neurolint16020030 - 5 Apr 2024
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Traumatic brain injuries (TBIs) represent a significant public health concern, with mild-to-moderate cases comprising a substantial portion of incidents. Understanding the predictors of mortality among adult patients with mild-to-moderate TBIs is crucial for optimizing clinical management and improving outcomes. This literature review examines
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Traumatic brain injuries (TBIs) represent a significant public health concern, with mild-to-moderate cases comprising a substantial portion of incidents. Understanding the predictors of mortality among adult patients with mild-to-moderate TBIs is crucial for optimizing clinical management and improving outcomes. This literature review examines the existing research to identify and analyze the mortality predictors in this patient population. Through a comprehensive review of peer-reviewed articles and clinical studies, key prognostic factors, such as age, Glasgow Coma Scale (GCS) score, the presence of intracranial hemorrhage, pupillary reactivity, and coexisting medical conditions, are explored. Additionally, this review investigates the role of advanced imaging modalities, biomarkers, and scoring systems in predicting mortality following a mild-to-moderate TBI. By synthesizing the findings from diverse studies, this review aims to provide clinicians and researchers with valuable insights into the factors influencing mortality outcomes in adult patients with a mild-to-moderate TBI, thus facilitating more informed decision making and targeted interventions in clinical practice.
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Open AccessArticle
Utilization of Ocrelizumab within Different Treatment Strategies for Multiple Sclerosis: A 5-Year Population-Based Study
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Marcello Moccia, Giuseppina Affinito, Giuseppina Marrazzo, Tiziana Ciarambino, Paolo Di Procolo, Licia Confalonieri, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Maria Triassi, Vincenzo Brescia Morra and Raffaele Palladino
Neurol. Int. 2024, 16(2), 394-405; https://doi.org/10.3390/neurolint16020029 - 29 Mar 2024
Abstract
Background: We aim to provide up-to-date real-world evidence on the persistence, adherence, healthcare resource utilization, and costs of multiple sclerosis (MS) by comparing ocrelizumab to other disease-modifying treatments (DMTs) and within different DMT sequences. Methods: We included 3371 people with MS who first
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Background: We aim to provide up-to-date real-world evidence on the persistence, adherence, healthcare resource utilization, and costs of multiple sclerosis (MS) by comparing ocrelizumab to other disease-modifying treatments (DMTs) and within different DMT sequences. Methods: We included 3371 people with MS who first received or switched DMT prescriptions from January 2018 to December 2022; they were identified through hospital discharge records, drug prescriptions, and exemption codes from the Campania Region (South Italy). We calculated persistence (time from the first prescription to discontinuation or switching to another DMT), adherence (proportion of days covered (PDC)), DMT costs, and MS hospital admissions and related costs. Results: The most frequently prescribed DMT was dimethyl fumarate (n = 815; age 38.90 ± 11.91 years; 69.5% females), followed by ocrelizumab (n = 682; age 46.46 ± 11.29 years; 56.3%); 28.8% of the patients treated with ocrelizumab were naïve to DMTs. Using ocrelizumab as a statistical reference, the risk of discontinuation was higher for other highly active (HR = 6.32; 95%CI = 3.16, 12.63; p < 0.01) and low-/medium-efficacy DMTs (HR = 10.10; 95%CI = 5.10, 19.77; p < 0.01); adherence was lower for other highly active DMTs (Coeff = −0.07; 95%CI = −0.10, −0.04; p < 0.01) and low-/medium-efficacy DMTs (Coeff = −0.16; 95%CI = −0.19, −0.14; p < 0.01). monthly DMT costs were higher for other highly active DMTs (Coeff = 77.45; 95%CI = 29.36, 125.53; p < 0.01) but lower for low-/medium-efficacy DMTs (Coeff = −772.31; 95%CI = −816.95, −727.66; p < 0.01). The hospital admissions and related costs of MS were similar between ocrelizumab, other highly active DMTs, and other low-/medium-efficacy DMTs, and with ocrelizumab as the first-line DMT after other highly active DMTs and after low-/medium-efficacy DMTs, which was possibly due to the low number of observations. Conclusions: From 2018 to 2022, ocrelizumab was among the most frequently prescribed DMTs, with 28.8% prescriptions to incident MS patients, confirming its relevance in clinical practice. Ocrelizumab was associated with the highest persistence and adherence, pointing towards its favorable benefit–risk profile. The costs of ocrelizumab were lower than those of other highly active DMTs.
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(This article belongs to the Special Issue Exclusive Papers from the Editorial Board Members (EBMs) and Invited Scholars of Neurology International)
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Open AccessReview
Decoding Post-Viral Fatigue: The Basal Ganglia’s Complex Role in Long-COVID
by
Thorsten Rudroff
Neurol. Int. 2024, 16(2), 380-393; https://doi.org/10.3390/neurolint16020028 - 28 Mar 2024
Abstract
Long-COVID afflicts millions with relentless fatigue, disrupting daily life. The objective of this narrative review is to synthesize current evidence on the role of the basal ganglia in long-COVID fatigue, discuss potential mechanisms, and highlight promising therapeutic interventions. A comprehensive literature search was
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Long-COVID afflicts millions with relentless fatigue, disrupting daily life. The objective of this narrative review is to synthesize current evidence on the role of the basal ganglia in long-COVID fatigue, discuss potential mechanisms, and highlight promising therapeutic interventions. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases. Mounting evidence from PET, MRI, and functional connectivity data reveals basal ganglia disturbances in long-COVID exhaustion, including inflammation, metabolic disruption, volume changes, and network alterations focused on striatal dopamine circuitry regulating motivation. Theories suggest inflammation-induced signaling disturbances could impede effort/reward valuation, disrupt cortical–subcortical motivational pathways, or diminish excitatory input to arousal centers, attenuating drive initiation. Recent therapeutic pilots targeting basal ganglia abnormalities show provisional efficacy. However, heterogeneous outcomes, inconsistent metrics, and perceived versus objective fatigue discrepancies temper insights. Despite the growing research, gaps remain in understanding the precise pathways linking basal ganglia dysfunction to fatigue and validating treatment efficacy. Further research is needed to advance understanding of the basal ganglia’s contribution to long-COVID neurological sequelae and offer hope for improving function across the expanding affected population.
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(This article belongs to the Special Issue COVID-19, Neuroinflammation and Therapeutics, 2nd Edition)
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Open AccessCommunication
Hyperglycaemia Aggravates Oxidised Low-Density Lipoprotein-Induced Schwann Cell Death via Hyperactivation of Toll-like Receptor 4
by
Wataru Nihei, Ayako Kato, Tatsuhito Himeno, Masaki Kondo, Jiro Nakamura, Hideki Kamiya, Kazunori Sango and Koichi Kato
Neurol. Int. 2024, 16(2), 370-379; https://doi.org/10.3390/neurolint16020027 - 19 Mar 2024
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Increased low-density lipoprotein levels are risk factors for diabetic neuropathy. Diabetes mellitus is associated with elevated metabolic stress, leading to oxidised low-density lipoprotein formation. Therefore, it is important to investigate the mechanisms underlying the pathogenesis of diabetic neuropathy in diabetes complicated by dyslipidaemia
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Increased low-density lipoprotein levels are risk factors for diabetic neuropathy. Diabetes mellitus is associated with elevated metabolic stress, leading to oxidised low-density lipoprotein formation. Therefore, it is important to investigate the mechanisms underlying the pathogenesis of diabetic neuropathy in diabetes complicated by dyslipidaemia with increased levels of oxidised low-density lipoprotein. Here, we examined the effects of hyperglycaemia and oxidised low-density lipoprotein treatment on Schwann cell death and its underlying mechanisms. Immortalised mouse Schwann cells were treated with oxidised low-density lipoprotein under normo- or hyperglycaemic conditions. We observed that oxidised low-density lipoprotein-induced cell death increased under hyperglycaemic conditions compared with normoglycaemic conditions. Moreover, hyperglycaemia and oxidised low-density lipoprotein treatment synergistically upregulated the gene and protein expression of toll-like receptor 4. Pre-treatment with TAK-242, a selective toll-like receptor 4 signalling inhibitor, attenuated hyperglycaemia- and oxidised low-density lipoprotein-induced cell death and apoptotic caspase-3 pathway. Our findings suggest that the hyperactivation of toll-like receptor 4 signalling by hyperglycaemia and elevated oxidised low-density lipoprotein levels synergistically exacerbated diabetic neuropathy; thus, it can be a potential therapeutic target for diabetic neuropathy.
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Depression and Anxiety Symptoms in Headache Disorders: An Observational, Cross-Sectional Study
by
Leonidas Mantonakis, Ioanna Belesioti, Christina I. Deligianni, Vasilis Natsis, Euthimia Mitropoulou, Elina Kasioti, Maria Lypiridou and Dimos D. Mitsikostas
Neurol. Int. 2024, 16(2), 356-369; https://doi.org/10.3390/neurolint16020026 - 18 Mar 2024
Abstract
Background: Headache disorders have been associated with anxiety and depressive disorders. The aim of this study was to assess symptoms of anxiety and depression in a large sample of individuals with different headache disorders (HDs) in order to determine whether their frequency differs
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Background: Headache disorders have been associated with anxiety and depressive disorders. The aim of this study was to assess symptoms of anxiety and depression in a large sample of individuals with different headache disorders (HDs) in order to determine whether their frequency differs by headache type. Methods: Consecutive individuals with headache attending a headache outpatient clinic were interviewed with the HAM-D and HAM-A, along with age, sex, and education matched non-headache individuals. Results: Individuals numbering 2673 with headache (females 71.2%) and 464 non-headache individuals (females 70.9%) were interviewed (with participation rates of 98.3% and 91.0%, respectively). Migraine was diagnosed in 49.7%, tension-type headache in 38%, cluster headache 5.2%, and medication overuse (MO) in 21.8%. Participants with HD scored more in HAM-A (OR = 4.741, CI95%: 3.855–5.831, p < 0.001) and HAM-D scales (OR = 2.319, CI95%: 1.892–2.842, p < 0.001) than non-headache individuals. Participants with chronic HDs (≥15 days with headache for ≥3 consecutive months; 52.5%) scored higher for both HAM-A (OR = 1.944, CI95%: 1.640–2.303, p < 0.001) and HAM-D (OR = 1.625, CI95%: 1.359–1.944, p < 0.001) than those with episodic HDs (33.1%), as did participants with MO vs. participants without MO (OR = 3.418, CI95%: 2.655–4.399, p < 0.001 for HAM-A, OR = 3.043, CI95%: 2.322–3.986, p < 0.001 for HAM-D). Female and low-educated participants scored higher on both scales. Conclusion: Because symptoms of anxiety and depression are substantial in people with HD, the treating physicians should look out for such symptoms and manage them appropriately.
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(This article belongs to the Special Issue Migraines and Beyond: Advances in the Pathogenesis and Treatment of Chronic Headache Disorders)
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Open AccessCase Report
Pulsed Radiofrequency for Auriculotemporal Neuralgia: A Case Report
by
Yan Tereshko, Enrico Belgrado, Christian Lettieri, Simone Dal Bello, Giovanni Merlino, Gian Luigi Gigli and Mariarosaria Valente
Neurol. Int. 2024, 16(2), 349-355; https://doi.org/10.3390/neurolint16020025 - 12 Mar 2024
Abstract
Auriculotemporal neuralgia is a rare facial pain disorder with no therapeutic evidence for refractory cases. We described a male patient with right auriculotemporal neuralgia, refractory to anesthetic nerve blocks and botulinum toxin type A injections, who was successfully treated with pulsed radiofrequency without
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Auriculotemporal neuralgia is a rare facial pain disorder with no therapeutic evidence for refractory cases. We described a male patient with right auriculotemporal neuralgia, refractory to anesthetic nerve blocks and botulinum toxin type A injections, who was successfully treated with pulsed radiofrequency without adverse events. Pulsed radiofrequency may be an effective and safe treatment for refractory auriculotemporal neuralgia.
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(This article belongs to the Special Issue Migraines and Beyond: Advances in the Pathogenesis and Treatment of Chronic Headache Disorders)
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