Neurology International

31 pages, 2588 KiB

Open AccessReview

Animal Models of Intervertebral Disc Diseases: Advantages, Limitations, and Future Directions

by Jin Young Hong, Hyunseong Kim, Wan-Jin Jeon, Changhwan Yeo, Hyun Kim, Junseon Lee, Yoon Jae Lee and In-Hyuk Ha

Neurol. Int. 2024, 16(6), 1788-1818; https://doi.org/10.3390/neurolint16060129 - 9 Dec 2024

Abstract

Animal models are valuable tools for studying the underlying mechanisms of and potential treatments for intervertebral disc diseases. In this review, we discuss the advantages and limitations of animal models of disc diseases, focusing on lumbar spinal stenosis, disc herniation, and degeneration, as [...] Read more.

Animal models are valuable tools for studying the underlying mechanisms of and potential treatments for intervertebral disc diseases. In this review, we discuss the advantages and limitations of animal models of disc diseases, focusing on lumbar spinal stenosis, disc herniation, and degeneration, as well as future research directions. The advantages of animal models are that they enable controlled experiments, long-term monitoring to study the natural history of the disease, and the testing of potential treatments. However, they also have limitations, including species differences, ethical concerns, a lack of standardized protocols, and short lifespans. Therefore, ongoing research focuses on improving animal model standardization and incorporating advanced imaging and noninvasive techniques, genetic models, and biomechanical analyses to overcome these limitations. These future directions hold potential for improving our understanding of the underlying mechanisms of disc diseases and for developing new treatments. Overall, although animal models can provide valuable insights into pathophysiology and potential treatments for disc diseases, their limitations should be carefully considered when interpreting findings from animal studies. Full article

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9 pages, 6226 KiB

Open AccessCase Report

Internal Ophthalmoplegic Migraine During Pregnancy: A Clinical Case

by Brenda Castillo-Guerrero, Gloria Londoño-Juliao, Yesenia Pianetta, Melissa Gutiérrez-Rey, Bley Jair Zuñiga, Gustavo Pestana, Ana-Karina Carbonell-Zabaleta, Diego Rivera-Porras, Valmore Bermúdez and José Vargas-Manotas

Neurol. Int. 2024, 16(6), 1779-1787; https://doi.org/10.3390/neurolint16060128 - 9 Dec 2024

Abstract

Background: Ophthalmoplegic migraine (OM) is an uncommon variant of migraine characterised by headache and cranial nerve palsy, posing significant diagnostic and therapeutic challenges. Objective: This study aimed to describe an extremely rare OM variant with a partial therapeutic response. Clinical Case: A 34-year-old [...] Read more.

Background: Ophthalmoplegic migraine (OM) is an uncommon variant of migraine characterised by headache and cranial nerve palsy, posing significant diagnostic and therapeutic challenges. Objective: This study aimed to describe an extremely rare OM variant with a partial therapeutic response. Clinical Case: A 34-year-old pregnant woman in gestational week 19.1 (G6P2A3) with a history of three consecutive spontaneous abortions presented at the emergency services with insidious onset and mild-to-moderate-intensity pulsatile bifrontal headache for 15 days, and the positional changes exacerbated this. At peak intensity, she experienced nausea, vomiting, tinnitus, and photophobia without phonophobia or osmophobia, prompting multiple visits to the emergency department. Despite a broad range of treatments, including intravenous fluids, analgesia, pericranial blocks, and preventive management, there was a non-significative improvement in the symptomatology described above. However, spontaneous resolution of this clinical picture was observed during the postpartum period. Results: This case highlights the complexity of ophthalmoplegic migraine, especially in the context of pregnancy, and raises questions about the underlying pathophysiological mechanisms. The absence of structural lesions on neuroimaging and postpartum resolution suggests a potential association with the hormonal and physiological changes associated with pregnancy. Conclusions: Despite limited scientific evidence, this report contributes to expanding the knowledge of this rare entity and emphasises the importance of a multidisciplinary approach to its management. Full article

(This article belongs to the Special Issue Migraines and Beyond: Advances in the Pathogenesis and Treatment of Chronic Headache Disorders, Second Edition)

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Graphical abstract

29 pages, 1782 KiB

Open AccessReview

Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection

by Marina Boziki, Paschalis Theotokis, Evangelia Kesidou, Maria Nella, Christos Bakirtzis, Eleni Karafoulidou, Maria Tzitiridou-Chatzopoulou, Michael Doulberis, Evangelos Kazakos, Georgia Deretzi, Nikolaos Grigoriadis and Jannis Kountouras

Neurol. Int. 2024, 16(6), 1750-1778; https://doi.org/10.3390/neurolint16060127 - 6 Dec 2024

Abstract

Background: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common [...] Read more.

Background: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise “primary cerebrovascular and neurodegenerative” disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction. Methods: This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. Results: In view of recent evidence that the gut–brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut–brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut–brain axis homeostasis towards local and systemic pro-inflammatory responses. Conclusion: As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field. Full article

(This article belongs to the Collection Advances in Neurodegenerative Diseases)

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8 pages, 2716 KiB

Open AccessCase Report

Management of Post-Traumatic Pseudomeningocele as Consequence of Root Nerve Avulsion: Case Report and Review of the Literature

by Leonardo Bradaschia, Filippo Lacatena, Francesca Vincitorio, Paolo Titolo, Bruno Battiston, Diego Garbossa and Fabio Cofano

Neurol. Int. 2024, 16(6), 1742-1749; https://doi.org/10.3390/neurolint16060126 - 6 Dec 2024

Abstract

Background: Post-traumatic pseudomeningoceles are common findings after a brachial or lumbar plexus trauma, in particular after nerve root avulsion. Unlike meningoceles, pseudomeningoceles are CSF full-filled cysts confined by the paraspinous soft tissue, along the normal nerve course, in communication with the spinal subarachnoid [...] Read more.

Background: Post-traumatic pseudomeningoceles are common findings after a brachial or lumbar plexus trauma, in particular after nerve root avulsion. Unlike meningoceles, pseudomeningoceles are CSF full-filled cysts confined by the paraspinous soft tissue, along the normal nerve course, in communication with the spinal subarachnoid spaces. Normally no more than a radiological finding at MRI, in rare instances they might be symptomatic due to their size or might constitute an obstacle during a reconstructive surgery. Methods: A review of the literature was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in a time span ranging from November 1972 to May 2024. A total of five articles were found meeting the inclusion criteria. A case report at our institution was added to the case history. Results: A 30-year-old man with complete right brachial plexus nerve roots avulsion and a voluminous pseudomeningocele at the C6-C7 level after a motorcycle incident in January 2023. The pseudomeningocele covered the entirety of the injured brachial plexus. Pre-operative external lumbar drainage was utilized to prevent relapse or worsening of the already existing cerebral spinal fluid collection, with good results at 6 months. The full case report is reported in detail. Conclusions: To date, no clear guidelines about the management of post-traumatic pseudomeningoceles are reported in the literature. The lack of symptoms or signs related to them does not usually require any surgical intervention. If not, a possible management strategy with the use of an external lumbar drainage is proposed, a solution already in use in other surgical contexts with successful results in preventing CSF fistula or its relapse. Full article

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11 pages, 8256 KiB

Open AccessArticle

Haloperidol-Induced Catalepsy and Its Correlations with Acetylcholinesterase Activity in Different Brain Structures of Mice

by Brenda Rufino da Silva, Joyce Maria Ferreira Alexandre Lima, Marcela Bermudez Echeverry and Carlos Alberto-Silva

Neurol. Int. 2024, 16(6), 1731-1741; https://doi.org/10.3390/neurolint16060125 - 5 Dec 2024

Abstract

Background/Objectives: Antipsychotic medicines are used to treat several psychological disorders and some symptoms caused by dementia and schizophrenia. Haloperidol (Hal) is a typical antipsychotic usually used to treat psychosis; however, its use causes motor or extrapyramidal symptoms (EPS) such as catalepsy. Hal blocks [...] Read more.

Background/Objectives: Antipsychotic medicines are used to treat several psychological disorders and some symptoms caused by dementia and schizophrenia. Haloperidol (Hal) is a typical antipsychotic usually used to treat psychosis; however, its use causes motor or extrapyramidal symptoms (EPS) such as catalepsy. Hal blocks the function of presynaptic D2 receptors on cholinergic interneurons, leading to the release of acetylcholine (ACh), which is hydrolyzed by the enzyme acetylcholinesterase (AChE). Methods: This study was designed to investigate the Hal-inhibitory effects on AChE activity in regions representative of the cholinergic system of mice and potential associations between cataleptic effects generated by Hal using therapeutic doses and their inhibitory effects on AChE. Results: The distribution of the AChE activity in the different regions of the brain followed the order striatum > hippocampus > (prefrontal cortex/hypothalamus/ cerebellum) > brainstem > septo-hippocampal system. In ex vivo assays, Hal inhibited AChE activity obtained from homogenate tissue of the striatum, hippocampus, and septo-hippocampal system in a concentration-dependent manner. The inhibitory concentration of 50% of enzyme activity (IC₅₀) indicated that the septo-hippocampal system required a higher concentration of Hal (IC₅₀ = 202.5 µmol·L⁻¹) to inhibit AChE activity compared to the striatum (IC₅₀ = 162.5 µmol·L⁻¹) and hippocampus (IC₅₀ = 145 µmol·L⁻¹). In in vivo assays, male Swiss mice treated with concentrations of Hal higher than 0.1 mg·kg⁻¹ induced cataleptic effects. Positive correlations with Spearman’s correlation were observed only between the lack of cataleptic effect and the decreased AChE activity of the hippocampus in the mice treated with 0.01 mg·kg⁻¹ of Hal but not in the striatum and septo-hippocampal system. Conclusions: Our results suggest that Hal could increase cholinergic effects via AChE inhibition, in addition to its dopamine antagonist effect, as an alternative approach to the treatment of behavioral disturbances associated with dementia. Full article

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14 pages, 917 KiB

Open AccessReview

New Insights into the Role of SGLT-2 Inhibitors in the Prevention of Dementia

by Cheng-Hsien Hung and Li-Yu Lu

Neurol. Int. 2024, 16(6), 1717-1730; https://doi.org/10.3390/neurolint16060124 - 5 Dec 2024

Abstract

Diabetes mellitus (DM) is a chronic disease associated with numerous complications, including cardiovascular diseases, nephropathy, and neuropathy. Sodium–glucose cotransporter 2 (SGLT-2) inhibitors, a class of novel antidiabetic agents, have demonstrated promising therapeutic effects beyond glycemic control, with potential benefits extending to the cardiovascular [...] Read more.

Diabetes mellitus (DM) is a chronic disease associated with numerous complications, including cardiovascular diseases, nephropathy, and neuropathy. Sodium–glucose cotransporter 2 (SGLT-2) inhibitors, a class of novel antidiabetic agents, have demonstrated promising therapeutic effects beyond glycemic control, with potential benefits extending to the cardiovascular and renal systems. Recently, research has increasingly focused on exploring the potential role of SGLT-2 inhibitors in preventing dementia. The aim of this review is to summarize the current research suggesting that SGLT-2 inhibitors, such as empagliflozin and dapagliflozin, may have neuroprotective effects that reduce dementia risk and improve cognitive function in type 2 diabetes patients. These benefits are likely due to better glycemic control, reduced oxidative stress, and less advanced glycation end-product (AGE) formation, all linked to neurodegeneration. Despite these promising findings, existing studies are limited by small sample sizes and short follow-up durations, which may not adequately capture long-term outcomes. To establish more robust evidence, larger-scale, long-term randomized controlled trials (RCTs) involving diverse populations are needed. These studies should involve diverse populations and focus on understanding the mechanisms behind the neuroprotective effects. Addressing these limitations will provide clearer guidelines for using SGLT-2 inhibitors in dementia prevention and management. This will help improve therapeutic strategies for cognitive health in diabetic patients. Full article

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26 pages, 1516 KiB

Open AccessReview

Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications

by Jonathan M. Borkum

Neurol. Int. 2024, 16(6), 1691-1716; https://doi.org/10.3390/neurolint16060123 - 4 Dec 2024

Abstract

Cluster headache is a severe, poorly understood disorder for which there are as yet virtually no rationally derived treatments. Here, Lee Kudrow’s 1983 theory, that cluster headache is an overly zealous response to hypoxia, is updated according to current understandings of hypoxia detection, [...] Read more.

Cluster headache is a severe, poorly understood disorder for which there are as yet virtually no rationally derived treatments. Here, Lee Kudrow’s 1983 theory, that cluster headache is an overly zealous response to hypoxia, is updated according to current understandings of hypoxia detection, signaling, and sensitization. It is shown that the distinctive clinical characteristics of cluster headache (circadian timing of attacks and circannual patterning of bouts, autonomic symptoms, and agitation), risk factors (cigarette smoking; male gender), triggers (alcohol; nitroglycerin), genetic findings (GWAS studies), anatomical substrate (paraventricular nucleus of the hypothalamus, solitary tract nucleus/NTS, and trigeminal nucleus caudalis), neurochemical features (elevated levels of galectin-3, nitric oxide, tyramine, and tryptamine), and responsiveness to treatments (verapamil, lithium, melatonin, prednisone, oxygen, and histamine desensitization) can all be understood in terms of hypoxic signaling. Novel treatment directions are hypothesized, including repurposing pharmacological antagonists of hypoxic signaling molecules (HIF-2; P2X3) for cluster headache, breath training, physical exercise, high-dose thiamine, carnosine, and the flavonoid kaempferol. The limits of current knowledge are described, and a program of basic and translational research is proposed. Full article

(This article belongs to the Special Issue Migraines and Beyond: Advances in the Pathogenesis and Treatment of Chronic Headache Disorders, Second Edition)

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17 pages, 818 KiB

Open AccessCase Report

Early Therapeutic Plasma Exchange in Pediatric Transverse Myelitis: A Case Report and Scoping Review

by Akram Khan, José Peña, Genesis Briceño, Juliann M. Gronquist, Khurram Khan, Raju Reddy, Vijayshree Yadav and Asha Singh

Neurol. Int. 2024, 16(6), 1674-1690; https://doi.org/10.3390/neurolint16060122 - 4 Dec 2024

Abstract

Background/Objectives: Transverse myelitis (TM) is a rare, acute inflammatory disorder affecting the spinal cord, with severe potential consequences, particularly in pediatric patients. Therapeutic plasma exchange (TPE) has emerged as a possible intervention for children unresponsive to high-dose corticosteroids. This study explores the efficacy [...] Read more.

Background/Objectives: Transverse myelitis (TM) is a rare, acute inflammatory disorder affecting the spinal cord, with severe potential consequences, particularly in pediatric patients. Therapeutic plasma exchange (TPE) has emerged as a possible intervention for children unresponsive to high-dose corticosteroids. This study explores the efficacy of early TPE in pediatric TM through a case report and scoping review aiming to clarify the therapeutic benefits of TPE when used in conjunction with corticosteroids in children. Methods: We present a scoping review of existing literature on the early administration of TPE in pediatric patients with TM, supplemented by a case report of a 5-year-old boy with Longitudinally Extensive Transverse Myelitis (LETM), who received early TPE and corticosteroid therapy. Clinical progression, response to TPE, and functional outcomes were documented over a 9-month follow-up period. Results: Among the reviewed cases, early TPE demonstrated potential to expedite neurological recovery and improve functional outcomes. In our case report, the patient showed rapid recovery, achieving unassisted ambulation by day four of TPE. No adverse effects were observed. MRI findings revealed substantial resolution of spinal cord lesions by three months, with near-complete symptom resolution at nine months. Conclusions: Early initiation of TPE, in conjunction with corticosteroids, may offer significant therapeutic benefit in pediatric TM, potentially accelerating recovery and improving outcomes. This case highlights the need for further controlled studies to establish evidence-based guidelines for TPE use in pediatric TM. Full article

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8 pages, 1939 KiB

Open AccessCase Report

Co-Existent Central and Peripheral Demyelination: Related or Coincidental?

by Camila Narvaez-Caicedo, Shireen M. Jacob, Laura Wu and Chilvana Patel

Neurol. Int. 2024, 16(6), 1666-1673; https://doi.org/10.3390/neurolint16060121 - 3 Dec 2024

Abstract

Background: Hereditary Sensory Motor Neuropathy (HSMN) 1A and Multiple Sclerosis (MS) are distinct demyelinating disorders affecting the peripheral and central nervous systems, respectively. We present a case of simultaneous occurrence of both conditions, exploring the clinical presentation, diagnostic workup, and potential interplay between [...] Read more.

Background: Hereditary Sensory Motor Neuropathy (HSMN) 1A and Multiple Sclerosis (MS) are distinct demyelinating disorders affecting the peripheral and central nervous systems, respectively. We present a case of simultaneous occurrence of both conditions, exploring the clinical presentation, diagnostic workup, and potential interplay between these diseases. Case presentation and clinical approach: A 49-year-old male with a history of optic neuritis presented with progressive numbness, weakness, and sensory loss in all extremities over four years. Neurological examination revealed distal weakness, sensory deficits in a stocking-glove distribution, pes cavus, and hammer toes. Nerve conduction studies and electromyography confirmed sensory motor demyelinating polyneuropathy. The patient’s lack of response to intravenous immunoglobulin therapy suggested hereditary neuropathy as an etiology. Genetic testing identified a PMP22 gene duplication, confirming HSMN 1A. Elevated cerebrospinal fluid protein level and oligoclonal bands, combined with magnetic resonance of the brain showing multiple T2 hyperintense lesions in the brain and spinal cord, fulfilled the diagnostic criteria for MS. Discussion: This case of co-existing HSMN 1A and MS highlights a rare overlap of peripheral and central demyelination. While HSMN 1A results from PMP22 gene duplication, primarily affecting peripheral myelin, MS is driven by immune-mediated central myelin attacks. The co-existence of these disorders suggests potential shared mechanisms, such as immune dysregulation. Some evidence suggests that overexpression of PMP22 in HSMN 1A may disturb immune tolerance, possibly triggering autoimmune responses linked to MS. Further research is needed to explore the genetic and autoimmune interplay between these two diseases, expanding our understanding of demyelinating disorders. Full article

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13 pages, 1547 KiB

Open AccessReview

Mechanisms of Neurosyphilis-Induced Dementia: Insights into Pathophysiology

by Aya Fadel, Hussain Hussain, Robert J. Hernandez, Amanda Marie Clichy Silva, Amir Agustin Estil-las, Mohammad Hamad, Zahraa F. Saadoon, Lamia Naseer, William C. Sultan, Carla Sultan, Taylor Schnepp and Arumugam R. Jayakumar

Neurol. Int. 2024, 16(6), 1653-1665; https://doi.org/10.3390/neurolint16060120 - 2 Dec 2024

Abstract

Neurosyphilis-induced dementia represents a severe manifestation of tertiary syphilis, characterized by cognitive and neuropsychiatric impairments. This condition arises from the progression of syphilis to the central nervous system, where the spirochete causes damage through invasion, chronic inflammation, and neurodegeneration. The pathophysiology involves chronic [...] Read more.

Neurosyphilis-induced dementia represents a severe manifestation of tertiary syphilis, characterized by cognitive and neuropsychiatric impairments. This condition arises from the progression of syphilis to the central nervous system, where the spirochete causes damage through invasion, chronic inflammation, and neurodegeneration. The pathophysiology involves chronic inflammatory responses, direct bacterial damage, and proteinopathies. Treponema pallidum triggers an inflammatory cascade, resulting in neuronal injury and synaptic dysfunction. Abnormal protein accumulations, including TAR DNA-binding protein 43 (TDP-43) and tau, contribute to neuronal loss and cognitive decline. Seizures, psychiatric symptoms, and motor deficits further complicate the progression of dementia. Diagnosis includes clinical assessment, cerebrospinal fluid analysis, and neuroimaging. Diagnostic tests include CSF-VDRL, FTA-ABS, and neuroimaging techniques such as MRI and PET scans, which help detect structural changes and confirm neurosyphilis. Management of neurosyphilis-induced dementia involves antibiotic therapy and psychotropic medications to address both infectious and symptomatic components. While penicillin remains the cornerstone of treatment, psychotropic agents, including haloperidol, risperidone, quetiapine, and divalproex sodium, can manage psychiatric symptoms. However, careful monitoring is required due to potential side effects and interactions with ongoing treatment. Overall, early diagnosis and comprehensive management are crucial for mitigating the cognitive and neuropsychiatric impairments associated with neurosyphilis-induced dementia. Full article

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Graphical abstract

17 pages, 1634 KiB

Open AccessArticle

Pretreatment Cranial Computed Tomography Perfusion Predicts Dynamic Cerebral Autoregulation Changes in Acute Hemispheric Stroke Patients Having Undergone Recanalizing Therapy: A Retrospective Study

by Lehel-Barna Lakatos, Manuel Bolognese, Mareike Österreich, Martin Müller and Grzegorz Marek Karwacki

Neurol. Int. 2024, 16(6), 1636-1652; https://doi.org/10.3390/neurolint16060119 - 25 Nov 2024

Abstract

Objectives: Blood pressure (BP) management is challenging in patients with acute ischemic supratentorial stroke undergoing recanalization therapy due to the lack of established guidelines. Assessing dynamic cerebral autoregulation (dCA) may address this need, as it is a bedside technique that evaluates the transfer [...] Read more.

Objectives: Blood pressure (BP) management is challenging in patients with acute ischemic supratentorial stroke undergoing recanalization therapy due to the lack of established guidelines. Assessing dynamic cerebral autoregulation (dCA) may address this need, as it is a bedside technique that evaluates the transfer function phase in the very low-frequency (VLF) range (0.02–0.07 Hz) between BP and cerebral blood flow velocity (CBFV) in the middle cerebral artery. This phase is a prognostically relevant parameter, with lower values associated with poorer outcomes. This study aimed to evaluate whether early cranial computed tomography perfusion (CTP) can predict this parameter. Methods: In this retrospective study, 165 consecutive patients with hemispheric strokes who underwent recanalizing therapy were included (median age: 73 years; interquartile range (IQR) 60–80; women: 43 (26%)). The cohort comprised 91 patients treated with intravenous thrombolysis (IV-lysis) alone (median National Institute of Health Stroke Scale (NIHSS) score: 5; IQR 3–7) and 74 patients treated with mechanical thrombectomy (median NIHSS: 15; IQR 9–18). Regression analysis was performed to assess the relationship between pretreatment CTP-derived ischemic penumbra and core stroke volumes and the dCA VLF phase, as well as CBFV assessed within the first 72 h post-stroke event. Results: Pretreatment penumbra volume was a significant predictor of the VLF phase (adjusted r² = 0.040; β = −0.001, 95% confidence interval (CI): −0.0018 to −0.0002, p = 0.02). Core infarct volume was a stronger predictor of CBFV (adjusted r² = 0.082; β = 0.205, 95% CI: 0.0968–0.3198; p = 0.0003) compared to penumbra volume (p = 0.01). Additionally, in the low-frequency range (0.07–0.20 Hz), CBFV and BP were inversely related to the gain, an index of vascular tone. Conclusion: CTP metrics appear to correlate with the outcome-relevant VLF phase and reactive hyperemic CBFV, which interact with BP to influence vascular tone and gain. These aspects of dCA could potentially guide BP management in patients with acute stroke undergoing recanalization therapy. However, further validation is required. Full article

(This article belongs to the Special Issue Treatment Strategy and Mechanism of Acute Ischemic Stroke)

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10 pages, 1265 KiB

Open AccessArticle

Evolution of Cognitive Disorders in Patients with Mild Cognitive Impairment (MCI) After Ischemic Stroke: Secondary Data Analysis from the Improved Health Care in Neurology and Psychiatry—Longer Life (IHCNP) Study

by Dragoș-Cătălin Jianu, Ligia Petrica, Traian Flavius Dan, Georgiana Munteanu, Bianca Bora, Sergiu Florin Arnăutu, Sorin Ursoniu, Diana Chira, Ștefan Strilciuc, Cristian Falup-Pecurariu and Dafin Fior Mureșanu

Neurol. Int. 2024, 16(6), 1626-1635; https://doi.org/10.3390/neurolint16060118 - 21 Nov 2024

Abstract

Background: The Improved Health Care in Neurology and Psychiatry—Longer Life (IHCNP) study was an 18-month prospective, observational, non-interventional research study focused on patients with mild cognitive impairment (MCI) following ischemic stroke. Objectives: Our secondary analysis of the IHCNP data aimed to document the [...] Read more.

Background: The Improved Health Care in Neurology and Psychiatry—Longer Life (IHCNP) study was an 18-month prospective, observational, non-interventional research study focused on patients with mild cognitive impairment (MCI) following ischemic stroke. Objectives: Our secondary analysis of the IHCNP data aimed to document the progression of MCI in this patient group. Methods: A total of 100 patients from Romania were recruited, all of whom underwent cognitive assessments using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Rey Auditory Verbal Learning Test (RAVLT). Clinical evaluations were also conducted as part of the study. Baseline cognitive scores were recorded, and subsequent follow-ups documented cognitive changes over time. Results: At baseline, cognitive scores indicated mild impairment, with averages of MMSE 25.41, MoCA 23.27, and RAVLT 33.63. By the end of the study, patients exhibited a significant cognitive decline, with MMSE scores dropping by 8.7%, MoCA by 10.0%, and RAVLT by 29.5% (p < 0.0001 for all measures), reflecting the progressive nature of MCI post-stroke. Conclusions: These findings highlight the importance of early diagnosis and intervention to mitigate cognitive decline in post-stroke patients. The study underscores the need for ongoing cognitive monitoring to improve patient outcomes and manage MCI progression effectively. Full article

(This article belongs to the Special Issue Emerging Issues in Vascular Cognitive Impairment)

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15 pages, 16719 KiB

Open AccessReview

Macamides as Potential Therapeutic Agents in Neurological Disorders

by Karin J. Vera-López, Gonzalo Davila-Del-Carpio and Rita Nieto-Montesinos

Neurol. Int. 2024, 16(6), 1611-1625; https://doi.org/10.3390/neurolint16060117 - 21 Nov 2024

Abstract

Therapeutic treatment of nervous system disorders has represented one of the significant challenges in medicine for the past several decades. Technological and medical advances have made it possible to recognize different neurological disorders, which has led to more precise identification of potential therapeutic [...] Read more.

Therapeutic treatment of nervous system disorders has represented one of the significant challenges in medicine for the past several decades. Technological and medical advances have made it possible to recognize different neurological disorders, which has led to more precise identification of potential therapeutic targets, in turn leading to research into developing drugs aimed at these disorders. In this sense, recent years have seen an increase in exploration of the therapeutic effects of various metabolites extracted from Maca (Lepidium meyenii), a plant native to the central alpine region of Peru. Among the most important secondary metabolites contained in this plant are macamides, molecules derived from N-benzylamides of long-chain fatty acids. Macamides have been proposed as active drugs to treat some neurological disorders. Their excellent human tolerance and low toxicity along with neuroprotective, immune-enhancing, and and antioxidant properties make them ideal for exploration as therapeutic agents. In this review, we have compiled information from various studies on macamides, along with theories about the metabolic pathways on which they act. Full article

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26 pages, 5841 KiB

Open AccessArticle

Sensitization and Habituation of Hyper-Excitation to Constant Presentation of Pattern-Glare Stimuli

by Thomas Jefferis, Cihan Dogan, Claire E. Miller, Maria Karathanou, Austyn Tempesta, Andrew J. Schofield and Howard Bowman

Neurol. Int. 2024, 16(6), 1585-1610; https://doi.org/10.3390/neurolint16060116 - 21 Nov 2024

Abstract

Background/Objectives: Pattern glare, associated with cortical hyperexcitability, induces visual distortions and discomfort, particularly in individuals susceptible to migraines or epilepsy. While previous research has primarily focused on transient EEG responses to patterned stimuli, this study aims to investigate how continuous presentation of pattern-glare [...] Read more.

Background/Objectives: Pattern glare, associated with cortical hyperexcitability, induces visual distortions and discomfort, particularly in individuals susceptible to migraines or epilepsy. While previous research has primarily focused on transient EEG responses to patterned stimuli, this study aims to investigate how continuous presentation of pattern-glare stimuli affects neural adaptation over both fine (seconds) and coarse (entire experiment) temporal scales. Methods: EEG recordings were obtained from 40 healthy participants exposed to horizontal square-wave gratings at three spatial frequencies presented continuously for three seconds each across multiple trials. Participants’ susceptibility to visual stress, headaches, and discomfort was assessed using questionnaires before and during the experiment. The experiment employed a two-by-two design to evaluate habituation (exponentially decreasing response) and sensitisation (exponentially increasing response) effects at two different time granularities. Mass univariate analysis with cluster-based permutation tests was conducted to identify significant brain response changes during the period of constant stimulation, which we call the DC-shift period. Results: Significant effects were observed during the DC-shift period, indicating sustained hyper-excitation to the medium-pattern glare stimulus. In particular, the mean/intercept analysis revealed a consistent positive-going response to the medium stimulus throughout the DC-shift period, suggesting continued neural engagement. Participants reporting higher discomfort exhibited sensitisation at fine temporal granularity and habituation at coarser temporal granularity. These effects were predominantly localised to the right posterior scalp regions. Conclusions: The study demonstrates that individuals sensitive to pattern-glare stimuli exhibit dynamic neural adaptation characterised by short-term sensitisation and long-term habituation. These findings enhance the understanding of cortical hyperexcitability mechanisms and may inform future interventions for visual-stress-related conditions, such as migraines and epilepsy. Further research is needed to explore the underlying neural processes and validate these effects in clinical populations. Full article

(This article belongs to the Special Issue Migraines and Beyond: Advances in the Pathogenesis and Treatment of Chronic Headache Disorders, Second Edition)

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33 pages, 1477 KiB

Open AccessReview

Mindfulness-Based Interventions and the Hypothalamic–Pituitary–Adrenal Axis: A Systematic Review

by Hernando Vargas-Uricoechea, Alejandro Castellanos-Pinedo, Karen Urrego-Noguera, Hernando D. Vargas-Sierra, María V. Pinzón-Fernández, Ernesto Barceló-Martínez and Andrés F. Ramírez-Giraldo

Neurol. Int. 2024, 16(6), 1552-1584; https://doi.org/10.3390/neurolint16060115 - 20 Nov 2024

Abstract

Background: Numerous studies have evaluated the effect that mindfulness-based interventions (MBIs) have on multiple health outcomes. For its part, stress is a natural response to environmental disturbances and within the associated metabolic responses, alterations in cortisol levels and their measurement in different tissues [...] Read more.

Background: Numerous studies have evaluated the effect that mindfulness-based interventions (MBIs) have on multiple health outcomes. For its part, stress is a natural response to environmental disturbances and within the associated metabolic responses, alterations in cortisol levels and their measurement in different tissues are a way to determine the stress state of an individual. Therefore, it has been proposed that MBIs can modify cortisol levels. Methods and results: The objective of this systematic review was to analyze and summarize the different studies that have evaluated the effect of MBIs on cortisol levels. The following databases were consulted: MEDLINE, AMED, CINAHL, Web of Science, Science Direct, PsycINFO, SocINDEX, PubMed, the Cochrane Library and Scopus. The search terms “mindfulness”, “mindfulness-based interventions” and “cortisol” were used (and the search was limited to studies from January 1990 to May 2024). In order to reduce selection bias, each article was scrutinized using the JBI Critical Appraisal Checklist independently by two authors. We included those studies with specified intervention groups with at least one control group and excluded duplicate studies or those in which the intervention or control group was not adequately specified. Significant changes in cortisol following MBIs were found in 25 studies, while 10 found no changes. The small sample size, lack of randomization, blinding, and probable confounding and interaction variables stand out in these studies. Conclusion: MBIs have biological plausibility as a means of explaining a positive effect on cortisol levels; however, the weakness of the studies and the absence of robust designs makes it difficult to establish a causal association between both variables. Registration number: INPLASY2024110017. Full article

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12 pages, 1354 KiB

Open AccessArticle

Slow Subcutaneous Release of Glatiramer Acetate or CD40-Targeting Peptide KGYY₆ Is More Advantageous in Treating Ongoing Experimental Autoimmune Encephalomyelitis

by Gisela M. Vaitaitis and David H. Wagner, Jr.

Neurol. Int. 2024, 16(6), 1540-1551; https://doi.org/10.3390/neurolint16060114 - 20 Nov 2024

Abstract

Background/Objectives: One of the first-line disease-modifying treatments of multiple sclerosis (MS) is Glatiramer Acetate (GA), which requires daily or three-times-weekly subcutaneous injections. Disease progression, while slowed, still occurs with time. Increasing the impact of the treatment while decreasing the frequency of injections would [...] Read more.

Background/Objectives: One of the first-line disease-modifying treatments of multiple sclerosis (MS) is Glatiramer Acetate (GA), which requires daily or three-times-weekly subcutaneous injections. Disease progression, while slowed, still occurs with time. Increasing the impact of the treatment while decreasing the frequency of injections would be ideal. The mechanism of action of GA remains undefined. We developed an alternate approach, KGYY₆, whose mechanism of action targets the CD40 receptor with promising results in an Experimental Autoimmune Encephalomyelitis (EAE) model. Methods: GA and a CD40-targeting peptide, KGYY₆, were formulated as slow-release particles used to treat EAE in C57BL/6 mice. Results: Compared to liquid formulations, the particle formulations vastly improved drug efficacy in both cases, which would be advantageous in treating MS. GA is a combination of randomly generated peptides, in the size range of 5000–9000 Da, using the amino acids E, A, Y, and K. This approach introduces batch differences that impacts efficacy, a persistent problem with GA. KGYY₆ is generated in a controlled process and has a motif, K-YY, which could be generated when manufacturing GA. When testing two different lots of GA or KGYY₆, the latter performed equally well across lots, while GA did not. Conclusions: Slow-release formulations of both GA and KGYY₆ vastly improve the efficacy of both, and KGYY₆ is more consistent in efficacy across different lots. Full article

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Graphical abstract

12 pages, 519 KiB

Open AccessArticle

Risk of Stroke or Heart Attack in Mild Cognitive Impairment and Subjective Cognitive Impairment

by Michele Lauriola, Luigi Esposito, Grazia D’Onofrio, Filomena Ciccone, Annamaria la Torre, Filomena Addante, Annagrazia Cocomazzi, Leandro Cascavilla, Olga Ariano, Gaetano Serviddio and Antonio Greco

Neurol. Int. 2024, 16(6), 1528-1539; https://doi.org/10.3390/neurolint16060113 - 19 Nov 2024

Abstract

Background: The study aimed to identify Mild Cognitive Impairment (MCI) as an alert clinical manifestation of increased probability of major acute vascular events (MVEs), such as Ischemic Stroke and heart attack. Methods: In a longitudinal study, 181 (M = 81, F = 100; [...] Read more.

Background: The study aimed to identify Mild Cognitive Impairment (MCI) as an alert clinical manifestation of increased probability of major acute vascular events (MVEs), such as Ischemic Stroke and heart attack. Methods: In a longitudinal study, 181 (M = 81, F = 100; mean age of 75.8 ± 8.69 years) patients were enrolled and divided into three groups based on diagnosis: Subjective Cognitive Impairment (SCI), amnestic MCI Single Domain (aMCI-SD), and amnestic MCI More Domain (aMCI-MD). Clinical assessment and the presence of vascular risk factors were collected. Results: The distribution of MVEs showed a higher incidence in the first two years of follow-up of 7.4% in SCI, 12.17% in aMCI-SD, and 8.57% in aMCI-MD. Acute Myocardial Infarction showed a major incidence in one year of follow-up (41%) and in two years of follow-up (29%). Also, Ischemic Stroke showed a major incidence in one year of follow-up (30%) and in two years of follow-up (40%). A statistically significant difference in the progression to dementia was shown (SCI 3.75%; aMCI-SD 10.43%; aMCI-MD 37%; p-value < 0.001). Conclusions: MCI is considered an expression of the systemic activation of mechanisms of endothelial damage, representing a diagnosis predictive of increased risk of MVEs. Full article

(This article belongs to the Special Issue Emerging Issues in Vascular Cognitive Impairment)

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19 pages, 1079 KiB

Open AccessReview

Mucuna pruriens, a Possible Treatment for Depressive Disorders

by Alfonso Mata-Bermudez, Araceli Diaz-Ruiz, Luis Ricardo Silva-García, Eduardo Manuel Gines-Francisco, Roxana Noriega-Navarro, Camilo Rios, Héctor Alonso Romero-Sánchez, Diego Arroyo, Abraham Landa and Luz Navarro

Neurol. Int. 2024, 16(6), 1509-1527; https://doi.org/10.3390/neurolint16060112 - 16 Nov 2024

Abstract

Depression is a mental disorder that depicts a wide variety of symptoms, including mood and cognitive alterations, as well as recurrent thoughts of death or suicide. It could become the second leading cause of premature death or disability worldwide. Treatments with conventional antidepressants [...] Read more.

Depression is a mental disorder that depicts a wide variety of symptoms, including mood and cognitive alterations, as well as recurrent thoughts of death or suicide. It could become the second leading cause of premature death or disability worldwide. Treatments with conventional antidepressants have several limitations in terms of effectiveness, side effects, and high costs. Therefore, medicinal plants such as Mucuna pruriens are potent candidates for treating depressive disorders. This review shows a compendium of evidence supporting the antidepressant effect of the Mucuna pruriens plant in diverse animal models. This includes the mechanisms of action underlying the antidepressant activity of the treatment concerning dopamine, serotonin, norepinephrine, reactive oxygen species, nitric oxide, cortisol, and inflammation. Clinical trials are needed to study the efficacy and safety of Mucuna pruriens for depression. Full article

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17 pages, 1302 KiB

Open AccessSystematic Review

The Neurological Impact of Leprosy: Manifestations and Treatment Approaches

by Andrea Calderone, Maria Catena Aloisi, Carmela Casella, Salvatore Fiannacca, Bruno Cosenza, Angelo Quartarone and Rocco Salvatore Calabrò

Neurol. Int. 2024, 16(6), 1492-1508; https://doi.org/10.3390/neurolint16060111 - 16 Nov 2024

Abstract

Background and Objectives: Leprosy primarily affects peripheral nerves, leading to significant neurological complications such as polyneuritis, mononeurosis, and autonomic dysfunction, which contribute to severe disabilities and impaired quality of life for patients. This scoping review aims to investigate the neurological manifestations and main [...] Read more.

Background and Objectives: Leprosy primarily affects peripheral nerves, leading to significant neurological complications such as polyneuritis, mononeurosis, and autonomic dysfunction, which contribute to severe disabilities and impaired quality of life for patients. This scoping review aims to investigate the neurological manifestations and main treatments of leprosy patients. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases. This review has been registered on OSF (n) PQBYH. Results: Neurological complications of leprosy, such as neuropathy and paralysis, necessitate accurate diagnosis and treatment, as immunological reactions can exacerbate nerve damage. Various studies highlight the effectiveness of personalized therapies, such as corticosteroids, multi-drug therapy (MDT), and surgical interventions, in improving symptoms and neurological function in leprosy patients. Conclusions: Managing neurological complications of leprosy necessitates careful diagnosis and treatment, as many patients experience unresolved peripheral neuropathy despite multidrug therapy. Future research should focus on improving diagnostic tools, exploring the link between neuropathic pain and psychological issues, and developing effective vaccines and treatments to enhance patient outcomes. Full article

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