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Neurol. Int., Volume 15, Issue 2 (June 2023) – 15 articles

Cover Story (view full-size image): The cognitive deficits of long-COVID include the dysfunction of the dorsolateral prefrontal cortex (dlPFC), which is especially vulnerable to inflammation. dlPFC neurotransmission requires NMDA and nicotinic α7 receptors, which are both blocked by kynurenic acid during inflammation. dlPFC neurons also express high levels of cAMP-calcium signaling during inflammation, opening K+ channels to reduce neuronal firing. These detrimental actions are lessened by agents that inhibit kynurenic acid production, e.g., N-acety-cysteine (NAC), and regulate cAMP-calcium-K+ channel signaling, e.g., the α2-adrenoceptor agonist, guanfacine. Guanfacine is also anti-inflammatory, deactivating glia, and NAC protects mitochondria from oxidative stress. Open label data suggest these agents can ameliorate the cognitive deficits of long-COVID, indicating a path forward for this debilitating disorder. View this paper
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14 pages, 1358 KiB  
Systematic Review
Gut Microbiota and Its Repercussion in Parkinson’s Disease: A Systematic Review in Occidental Patients
by Ana Cristina Proano, Javier A. Viteri, Eileen N. Orozco, Marco Antonio Calle, Stefany Carolina Costa, Daniel V. Reyes, Melissa German-Montenegro, David F. Moncayo, Andrea C. Tobar and Juan A. Moncayo
Neurol. Int. 2023, 15(2), 750-763; https://doi.org/10.3390/neurolint15020047 - 13 Jun 2023
Cited by 3 | Viewed by 2002
Abstract
(1) Background: Parkinson’s disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the [...] Read more.
(1) Background: Parkinson’s disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the occidental hemisphere, compare it, and search for any significant association between Parkinson’s disease and gut microbiota dysbiosis. (2) Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocols were used for this systematic review. PubMed was used as the database search engine. Of the 166 studies found, only 10 were used, as they met our inclusion criteria: case–control studies, studies that assessed the correlation of PD and gut microbiome, studies that took place in occidental regions, and studies that were performed on humans and were written in English. The Newcastle–Ottawa Scale was used as the assessment tool for overall risk of bias in this systematic review. (3) Results: The studies analyzed were divided into three geographic areas: Region 1: United States of America and Canada; Region 2: Germany, Ireland, and Finland; and Region 3: Italy; based on geographical similarities among these populations. The following statistically significant results were described in PD patients, compared with non-PD controls. In the first region, a significant increase in the following bacteria was seen: 1. Phylum: Actinobacteriota and its Genus: Bifidobacterium; 2. Phylum: Verrucomicrobiota and its Genus: Akkermansia; 3. Genus: Enterococcus, Hungatella, Lactobacillus, and Oscillospira of the Phylum: Firmicutes; 4. Family: Ruminococcaceae of Phylum: Firmicutes; 5. Phylum: Bacteroidetes and its Genus: Bacteroides; 6. Phylum: Proteobacteria. A significant decrease was described in the Family: Lachnospiraceae and its Genus: Blautia, Coprococcus, and Roseburia, which belong to the Phylum: Firmicutes. In the second region, a raised number of: 1. Phylum: Verrucomicrobiota, its Genus: Akkermansia, and its Species: Akkermansia muciniphila; 2. Family: Verrucomicrobiaceae of the Phylum: Verrucomicrobiota; 3. Genus: Lactobacillus and Roseburia of the Phylum: Firmicutes; 4. Family: Lactobacillaceae of the Phylum: Firmicutes; 5. Family: Barnesiellaceae of the Phylum: Bacteroidetes; 6. Genus: Bifidobacterium of the Phylum: Actinobacteriota; 7. Species: Bilophila wadsworthia of the Phylum: Thermodesulfobacteriota, was identified. Only one Genus: Prevotella of the Phylum: Bacteroidetes was decreased. In the third and last region, an augmented number of these bacteria were found: 1. Phylum: Verrucomicrobiota and its Genus: Akkermansia; 2. Family: Bifidobacteriaceae and Coriobacteriaceae of the Phylum: Actinobacteriota; 3. Phylum: Firmicutes and its Family: Christensenellaceae and Lactobacillaceae; 4. Family: Enterococcaceae and its Genus: Enterococcus, of the Phylum: Firmicutes; 5. Genus: Lactococcus and Oscillospira, of the Phylum: Firmicutes; 6. Phylum: Proteobacteria, its Family: Enterobacteriaceae, and the Genus: Citrobacter, Klebsiella, Salmonella, and Shigella; 7. Genus: ParaBacteroides of the Phylum: Bacteroidetes. In contrast, a significant decrease in 1. Phylum: Firmicutes, its Family: Lachnospiraceae, and its Genus: Roseburia and 2. Genus: Ruminococcus of the Phylum: Firmicutes, was described. (4) Conclusion: A significant gut dysbiosis, involving multiple bacterial taxa, was found in PD patients compared to healthy people in the occidental regions. However, more studies are needed to find the precise pathophysiologic involvement of other groups of pathogens, such as fungi and parasites, in the development and progression of PD. Full article
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7 pages, 250 KiB  
Brief Report
What Do Arithmetic Errors in the Financial Context Reveal? A Preliminary Study of Individuals with Neurocognitive Disorders
by Vaitsa Giannouli and Magdalini Tsolaki
Neurol. Int. 2023, 15(2), 743-749; https://doi.org/10.3390/neurolint15020046 - 1 Jun 2023
Viewed by 1293
Abstract
Objectives: Arithmetic errors in the financial context have been investigated mainly in cognitively normal Parkinson’s disease (PD) patients and mildly impaired PD (PD-MCI) individuals. The aim of this study was to examine arithmetic errors in the financial context across neurocognitive disorders. Methods: Four [...] Read more.
Objectives: Arithmetic errors in the financial context have been investigated mainly in cognitively normal Parkinson’s disease (PD) patients and mildly impaired PD (PD-MCI) individuals. The aim of this study was to examine arithmetic errors in the financial context across neurocognitive disorders. Methods: Four hundred and twenty older adults from Greece were divided into four groups (110 patients with a diagnosis of Alzheimer’s disease (AD), 107 patients with a diagnosis of mild cognitive impairment (MCI), 109 healthy controls and 94 Parkinson’s disease dementia (PDD) patients). Their ages ranged from 65 to 98 years (M = 73.96, SD = 6.68), and the sample had a mean of 8.67 (SD = 4.08) years of education. For each of the AD patients, a counterpart matched by age, educational attainment and gender was selected from a larger group of participants. Results: Overall, the results reveal that healthy older adults did not commit arithmetic errors, but AD patients reported procedural errors in their responses to both questions. A high frequency of procedural errors was found in MCI patients’ responses to the first question, while the errors in their responses to the second question cannot be categorized. Finally, in PDD patients, place value errors were reported for the first question, while more magnitude errors were made when responding to the second question. Conclusions: These findings support that arithmetic errors within financial contexts are not the same across neurocognitive disorders, and numerical representations are not impaired not only in PDD, but also in AD and MCI. This information could be useful in cognitive assessments performed by neurologists and neuropsychologists as these types of errors may be indicators of specific brain pathologies. Full article
(This article belongs to the Special Issue Global Burden of Neurological Disorder)
18 pages, 3053 KiB  
Review
Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID
by Arman Fesharaki Zadeh, Amy F. T. Arnsten and Min Wang
Neurol. Int. 2023, 15(2), 725-742; https://doi.org/10.3390/neurolint15020045 - 31 May 2023
Cited by 7 | Viewed by 6837
Abstract
Sustained cognitive deficits are a common and debilitating feature of “long COVID”, but currently there are no FDA-approved treatments. The cognitive functions of the dorsolateral prefrontal cortex (dlPFC) are the most consistently afflicted by long COVID, including deficits in working memory, motivation, and [...] Read more.
Sustained cognitive deficits are a common and debilitating feature of “long COVID”, but currently there are no FDA-approved treatments. The cognitive functions of the dorsolateral prefrontal cortex (dlPFC) are the most consistently afflicted by long COVID, including deficits in working memory, motivation, and executive functioning. COVID-19 infection greatly increases kynurenic acid (KYNA) and glutamate carboxypeptidase II (GCPII) in brain, both of which can be particularly deleterious to PFC function. KYNA blocks both NMDA and nicotinic-alpha-7 receptors, the two receptors required for dlPFC neurotransmission, and GCPII reduces mGluR3 regulation of cAMP-calcium-potassium channel signaling, which weakens dlPFC network connectivity and reduces dlPFC neuronal firing. Two agents approved for other indications may be helpful in restoring dlPFC physiology: the antioxidant N-acetyl cysteine inhibits the production of KYNA, and the α2A-adrenoceptor agonist guanfacine regulates cAMP-calcium-potassium channel signaling in dlPFC and is also anti-inflammatory. Thus, these agents may be helpful in treating the cognitive symptoms of long COVID. Full article
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17 pages, 661 KiB  
Article
Spatial and Temporal Gait Characteristics in Patients Admitted to a Neuro-Rehabilitation Department with Age-Related White Matter Changes: A Gait Analysis and Clinical Study
by Andrea Gagliardo, Antonello Grippo, Vincenzo Di Stefano, Riccardo Carrai, Maenia Scarpino, Monica Martini, Catiuscia Falsini, Giulia Rimmaudo and Filippo Brighina
Neurol. Int. 2023, 15(2), 708-724; https://doi.org/10.3390/neurolint15020044 - 25 May 2023
Viewed by 1653
Abstract
Background: Patients with age-related white matter changes (ARWMC) frequently present a gait disorder, depression and cognitive impairment. Our aims are to define which alterations in the gait parameters are associated with motor or neuro-psychological impairment and to assess the role of motor, mood [...] Read more.
Background: Patients with age-related white matter changes (ARWMC) frequently present a gait disorder, depression and cognitive impairment. Our aims are to define which alterations in the gait parameters are associated with motor or neuro-psychological impairment and to assess the role of motor, mood or cognitive dysfunction in explaining the variance of the gait parameters. Methods: Patients with gait disorders admitted to a Neuro-rehabilitation Department, affected by vascular leukoencephalopathy who had ARWMC confirmed by a brain MRI, were consecutively enrolled, classified by a neuroradiological scale (Fazekas 1987) and compared to healthy controls. We excluded subjects unable to walk independently, subjects with hydrocephalus or severe aphasia, with orthopaedic and other neurological pathologies conditioning the walking pattern. Patients and controls were assessed by clinical and functional scales (Mini Mental State Examination, Geriatric Depression Scale, Nevitt Motor Performance Scale, Berg Balance Scale, Functional Independence Measure), and computerised gait analysis was performed to assess the spatial and temporal gait parameters in a cross-sectional study. Results: We recruited 76 patients (48 males, aged 78.3 ± 6.2 years) and 14 controls (6 males, aged 75.8 ± 5 years). In the multiple regression analysis, the gait parameter with overall best model summary values, associated with the ARWMC severity, was the stride length even after correction for age, sex, weight and height (R2 = 0.327). The motor performances justified at least in part of the gait disorder (R2 change = 0.220), but the mood state accounted independently for gait alterations (R2 change = 0.039). The increase in ARWMC severity, the reduction of motor performance and a depressed mood state were associated with a reduction of stride length (R = 0.766, R2 = 0.587), reduction of gait speed (R2 = 0.573) and an increase in double support time (R2 = 0.421). Conclusion: The gait disorders in patients with ARWMC are related to motor impairment, but the presence of depression is an independent factor for determining gait alterations and functional status. These data pave the way for longitudinal studies, including gait parameters, to quantitatively assess gait changes after treatment or to monitor the natural progression of the gait disorders. Full article
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11 pages, 291 KiB  
Review
The Role of Alpha-2 Agonists for Attention Deficit Hyperactivity Disorder in Children: A Review
by Elisa E. Neuchat, Brooke E. Bocklud, Kali Kingsley, William T. Barham, Patrick M. Luther, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett and Alan D. Kaye
Neurol. Int. 2023, 15(2), 697-707; https://doi.org/10.3390/neurolint15020043 - 22 May 2023
Cited by 3 | Viewed by 7510
Abstract
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can [...] Read more.
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications’ long-term safety and efficacy remain uncertain, with a lack of data on their effects on growth, cardiovascular function, and other adverse events. Further studies are required to determine these medications’ optimal dose and treatment duration. Methods: Medications that target the noradrenergic system, such as Alpha-2 agonists, have been increasingly used as a treatment option for ADHD, with guanfacine and clonidine being two of the most commonly used medications. They function by selectively targeting Alpha-2 adrenergic receptors in the brain leading to improved attention and reduced hyperactivity and impulsivity symptoms in children with ADHD. Results: Clinical trials have demonstrated the effectiveness of Alpha-2 agonists in treating ADHD in children by reducing symptoms of inattention, hyperactivity, and impulsivity. However, these medications’ long-term safety and efficacy still need to be completely understood. Due to a lack of information on the effects of Alpha-2 agonists on growth, cardiovascular function, and other long-term adverse events, more studies must investigate the optimal dose and treatment duration for these medications. Conclusions: Despite these concerns, Alpha-2 agonists remain a valuable treatment option for ADHD in children, especially those unable to tolerate stimulant medications or who have coexisting conditions such as tic disorders. Future research should continue to explore the safety and efficacy of Alpha-2 agonists in the long term. In conclusion, Alpha-2 agonists show promise as a treatment for ADHD in children; however, the safety and efficacy of these drugs in the long term are not yet completely understood. Additional studies are required to investigate the optimal dose and treatment duration for these medications in their use as a treatment for this debilitating disease. Full article
36 pages, 980 KiB  
Systematic Review
Exploring the Utility of Autonomic Nervous System Evaluation for Stroke Prognosis
by Ilias Orgianelis, Ermis Merkouris, Sofia Kitmeridou, Dimitrios Tsiptsios, Stella Karatzetzou, Anastasia Sousanidou, Aimilios Gkantzios, Foteini Christidi, Efthymia Polatidou, Anastasia Beliani, Anna Tsiakiri, Christos Kokkotis, Stylianos Iliopoulos, Konstantinos Anagnostopoulos, Nikolaos Aggelousis and Konstantinos Vadikolias
Neurol. Int. 2023, 15(2), 661-696; https://doi.org/10.3390/neurolint15020042 - 16 May 2023
Cited by 2 | Viewed by 2226
Abstract
Stroke is a major cause of functional disability and is increasing in frequency. Therefore, stroke prognosis must be both accurate and timely. Among other biomarkers, heart rate variability (HRV) is investigated in terms of prognostic accuracy within stroke patients. The literature research of [...] Read more.
Stroke is a major cause of functional disability and is increasing in frequency. Therefore, stroke prognosis must be both accurate and timely. Among other biomarkers, heart rate variability (HRV) is investigated in terms of prognostic accuracy within stroke patients. The literature research of two databases (MEDLINE and Scopus) is performed to trace all relevant studies published within the last decade addressing the potential utility of HRV for stroke prognosis. Only the full-text articles published in English are included. In total, forty-five articles have been traced and are included in the present review. The prognostic value of biomarkers of autonomic dysfunction (AD) in terms of mortality, neurological deterioration, and functional outcome appears to be within the range of known clinical variables, highlighting their utility as prognostic tools. Moreover, they may provide additional information regarding poststroke infections, depression, and cardiac adverse events. AD biomarkers have demonstrated their utility not only in the setting of acute ischemic stroke but also in transient ischemic attack, intracerebral hemorrhage, and traumatic brain injury, thus representing a promising prognostic tool whose clinical application may greatly facilitate individualized stroke care. Full article
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12 pages, 1490 KiB  
Article
Cognitive Test Solution in Mice with Different Brain Weights after Atomoxetine
by Olga V. Perepelkina and Inga I. Poletaeva
Neurol. Int. 2023, 15(2), 649-660; https://doi.org/10.3390/neurolint15020041 - 15 May 2023
Viewed by 1408
Abstract
In this paper, the data are presented concerning different reactions to seven daily injections of atomoxetine in two mouse strains differing in relative brain weight. Atomoxetine affected the performance in a puzzle-box cognitive test in a complicated way—the large brain mice were less [...] Read more.
In this paper, the data are presented concerning different reactions to seven daily injections of atomoxetine in two mouse strains differing in relative brain weight. Atomoxetine affected the performance in a puzzle-box cognitive test in a complicated way—the large brain mice were less successful at task solutions (presumably because they were not afraid of the brightly lit test box), while the small brain strain of atomoxetine treated mice solved the task more successfully. The behavior of all atomoxetine treated animals was more active in an aversive situation (an unescapable slippery funnel, (analogous to the Porsolt test) and the time of immobility decreased significantly in all atomoxetine treated mice. The general patterns of behavioral reactions to atomoxetine in the cognitive test and other interstrain differences demonstrated in these experiments made it possible to suggest that differences in ascending noradrenergic projections between the two strains used exist. Further analysis of the noradrenergic system in these strains is needed (and further analysis of the effects of drugs which affect noradrenergic receptors). Full article
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11 pages, 694 KiB  
Article
Depression Severity Is Different in Dysosmic Patients Who Have Experienced Traumatic Brain Injury Compared with Those Who Have Not
by Agnieszka Sabiniewicz, Kyri-Kristin Lindner, Antje Haehner and Thomas Hummel
Neurol. Int. 2023, 15(2), 638-648; https://doi.org/10.3390/neurolint15020040 - 12 May 2023
Cited by 1 | Viewed by 1298
Abstract
Traumatic brain injury (TBI) in humans can result in olfactory, cognitive, and affective changes. Surprisingly, research on the consequences of TBI often did not control for olfactory function in the investigated groups. Consequently, the affective or cognitive differences might be misleading as related [...] Read more.
Traumatic brain injury (TBI) in humans can result in olfactory, cognitive, and affective changes. Surprisingly, research on the consequences of TBI often did not control for olfactory function in the investigated groups. Consequently, the affective or cognitive differences might be misleading as related rather to different olfactory performance than to a TBI experience. Hence, our study aimed to investigate whether TBI occurrence would lead to altered affective and cognitive functioning in two groups of dysosmic patients, one with TBI experience and one without. In total, 51 patients with TBI experience and 50 controls with varied causes of olfactory loss were thoroughly examined in terms of olfactory, cognitive, and affective performance. Student t-tests demonstrated that the only significant difference between the groups appeared in the depression severity, with TBI patients being more depressed (t = 2.3, p = 0.011, Cohen’s d = −0.47). Regression analyses further showed that TBI experience was significantly associated with depression severity (R2 = 0.05, F [1, 96] = 5.5, p = 0.021, beta = 1.4). In conclusion, the present study showed that TBI experience is linked to depression, which is more pronounced compared to individuals with olfactory loss without TBI. Full article
(This article belongs to the Special Issue Recent Advances in Traumatic Brain Injury)
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16 pages, 3130 KiB  
Article
Semi-Automated Recording of Facial Sensitivity in Rat Demonstrates Antinociceptive Effects of the Anti-CGRP Antibody Fremanezumab
by Nicola Benedicter, Karl Messlinger, Birgit Vogler, Kimberly D. Mackenzie, Jennifer Stratton, Nadine Friedrich and Mária Dux
Neurol. Int. 2023, 15(2), 622-637; https://doi.org/10.3390/neurolint15020039 - 29 Apr 2023
Cited by 3 | Viewed by 1924
Abstract
Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically [...] Read more.
Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically used in chronic and episodic migraines, can modify facial sensitivity recorded by a semi-automatic system. Rats of both sexes primed to drink from a sweet source had to pass a noxious mechanical or heat barrier to reach the source. Under these experimental conditions, animals of all groups tended to drink longer and more when they had received a subcutaneous injection of 30 mg/kg fremanezumab compared to control animals injected with an isotype control antibody 12–13 days prior to testing, but this was significant only for females. In conclusion, anti-CGRP antibody, fremanezumab, reduces facial sensitivity to noxious mechanical and thermal stimulation for more than one week, especially in female rats. Anti-CGRP antibodies may reduce not only headache but also cranial sensitivity in migraineurs. Full article
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13 pages, 2511 KiB  
Article
Posttraumatic and Idiopathic Spike–Wave Discharges in Rats: Discrimination by Morphology and Thalamus Involvement
by Ilia Komoltsev, Olga Salyp, Aleksandra Volkova, Daria Bashkatova, Natalia Shirobokova, Stepan Frankevich, Daria Shalneva, Olga Kostyunina, Olesya Chizhova, Pavel Kostrukov, Margarita Novikova and Natalia Gulyaeva
Neurol. Int. 2023, 15(2), 609-621; https://doi.org/10.3390/neurolint15020038 - 27 Apr 2023
Viewed by 1755
Abstract
The possibility of epileptiform activity generation by the thalamocortical neuronal network after focal brain injuries, including traumatic brain injury (TBI), is actively debated. Presumably, posttraumatic spike–wave discharges (SWDs) involve a cortico-thalamocortical neuronal network. Differentiation of posttraumatic and idiopathic (i.e., spontaneously generated) SWDs is [...] Read more.
The possibility of epileptiform activity generation by the thalamocortical neuronal network after focal brain injuries, including traumatic brain injury (TBI), is actively debated. Presumably, posttraumatic spike–wave discharges (SWDs) involve a cortico-thalamocortical neuronal network. Differentiation of posttraumatic and idiopathic (i.e., spontaneously generated) SWDs is imperative for understanding posttraumatic epileptogenic mechanisms. Experiments were performed on male Sprague-Dawley rats with electrodes implanted into the somatosensory cortex and the thalamic ventral posterolateral nucleus. Local field potentials were recorded for 7 days before and 7 days after TBI (lateral fluid percussion injury, 2.5 atm). The morphology of 365 SWDs (89 idiopathic before craniotomy, and 262 posttraumatic that appeared only after TBI) and their appearance in the thalamus were analyzed. The occurrence of SWDs in the thalamus determined their spike–wave form and bilateral lateralization in the neocortex. Posttraumatic discharges were characterized by more “mature” characteristics as compared to spontaneously generated discharges: higher proportions of bilateral spreading, well-defined spike–wave form, and thalamus involvement. Based on SWD parameters, the etiology could be established with an accuracy of 75% (AUC 0.79). Our results support the hypothesis that the formation of posttraumatic SWDs involves a cortico-thalamocortical neuronal network. The results form a basis for further research of mechanisms associated with posttraumatic epileptiform activity and epileptogenesis. Full article
(This article belongs to the Special Issue Recent Advances in Traumatic Brain Injury)
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14 pages, 1173 KiB  
Review
Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment
by Nicola Montemurro, Bhavya Pahwa, Anish Tayal, Anushruti Shukla, Manuel De Jesus Encarnacion, Issael Ramirez, Renat Nurmukhametov, Vishal Chavda and Antonella De Carlo
Neurol. Int. 2023, 15(2), 595-608; https://doi.org/10.3390/neurolint15020037 - 23 Apr 2023
Cited by 21 | Viewed by 2963
Abstract
Glioblastoma (GBM) is a common and highly malignant primary tumor of the central nervous system in adults. Ever more recent papers are focusing on understanding the role of the tumor microenvironment (TME) in affecting tumorigenesis and the subsequent prognosis. We assessed the impact [...] Read more.
Glioblastoma (GBM) is a common and highly malignant primary tumor of the central nervous system in adults. Ever more recent papers are focusing on understanding the role of the tumor microenvironment (TME) in affecting tumorigenesis and the subsequent prognosis. We assessed the impact of macrophages in the TME on the prognosis in patients with recurrent GBM. A PubMed, MEDLINE and Scopus review was conducted to identify all studies dealing with macrophages in the GBM microenvironment from January 2016 to December 2022. Glioma-associated macrophages (GAMs) act critically in enhancing tumor progression and can alter drug resistance, promoting resistance to radiotherapy and establishing an immunosuppressive environment. M1 macrophages are characterized by increased secretion of proinflammatory cytokines, such as IL-1ß, tumor necrosis factor (TNF), IL-27, matrix metalloproteinase (MMPs), CCL2, and VEGF (vascular endothelial growth factor), IGF1, that can lead to the destruction of the tissue. In contrast, M2 is supposed to participate in immunosuppression and tumor progression, which is formed after being exposed to the macrophage M-CSF, IL-10, IL-35 and the transforming growth factor-ß (TGF-β). Because there is currently no standard of care in recurrent GBM, novel identified targeted therapies based on the complex signaling and interactions between the glioma stem cells (GSCs) and the TME, especially resident microglia and bone-marrow-derived macrophages, may be helpful in improving the overall survival of these patients in the near future. Full article
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15 pages, 3210 KiB  
Article
Sensory Motor Function Disturbances in Mice Prenatally Exposed to Low Dose of Ethanol: A Neurobehavioral Study in Postnatal and Adult Stages
by Kamal Smimih, Bilal El-Mansoury, Fatima Ez-Zahraa Saad, Manal Khanouchi, Souad El Amine, Abdelmohcine Aimrane, Nadia Zouhairi, Abdessalam Ferssiwi, Abdelali Bitar, Mohamed Merzouki and Omar El Hiba
Neurol. Int. 2023, 15(2), 580-594; https://doi.org/10.3390/neurolint15020036 - 19 Apr 2023
Viewed by 1959
Abstract
Prenatal alcohol exposure (PAE) refers to fetal exposure to alcohol during pregnancy through placental barrier transfer from maternal blood. The postnatal outcomes of PAE differ among exposed individuals and range from overt (serious) alcohol-related behavioral and neurophysiological impairments to covert (silenced) symptoms. The [...] Read more.
Prenatal alcohol exposure (PAE) refers to fetal exposure to alcohol during pregnancy through placental barrier transfer from maternal blood. The postnatal outcomes of PAE differ among exposed individuals and range from overt (serious) alcohol-related behavioral and neurophysiological impairments to covert (silenced) symptoms. The aims of the present investigation were to assess the postnatal neurobehavioral disturbances, particularly, motor coordination and sensory-motor function in mice with PAE. Female mice with positive vaginal plugs were divided into three groups: group 1: Et + Pyr: received two i.p injections of ethanol (1 g/kg) followed by pyrazole (100 mg/kg). Group 2: Pyr: received an i.p injection of pyrazole (100 mg/kg). Group 3: C: of saline controls received, in equal volume, saline solution (NaCl 0.9%). After birth, mice pups were weighed and subjected to behavioral tests for motor function screening using the motor ambulation test, cliff aversion, surface righting, and negative geotaxis, while at the adult stage, mice were subjected to the open field, rotarod, parallel bars, and static rods tests. Our data show an obvious decrement of body weight from the first post-natal day (P1) and continues over the adult stage. This was accompanied by an obvious impaired sensory-motor function which was maintained even at the adult stage with alteration of the locomotor and coordination abilities. The current data demonstrate the powerful neurotoxic effect of prenatal ethanol exposure on the sensory-motor and coordination functions, leading to suppose possible structural and/or functional neuronal disturbances, particularly the locomotor network. Full article
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11 pages, 3284 KiB  
Case Report
Post-Polio Syndrome Revisited
by Michael Punsoni, Nelli S. Lakis, Michelle Mellion and Suzanne M. de la Monte
Neurol. Int. 2023, 15(2), 569-579; https://doi.org/10.3390/neurolint15020035 - 13 Apr 2023
Cited by 2 | Viewed by 4108
Abstract
Post-polio syndrome (PPS) is characterized by recrudescence or worsening of motor neuron disease symptoms decades after recovery from acute paralytic poliovirus infection, i.e., poliomyelitis. PPS afflicts between 25% and 40% of poliomyelitis survivors and mimics motor neuron diseases (MNDs), such as amyotrophic lateral [...] Read more.
Post-polio syndrome (PPS) is characterized by recrudescence or worsening of motor neuron disease symptoms decades after recovery from acute paralytic poliovirus infection, i.e., poliomyelitis. PPS afflicts between 25% and 40% of poliomyelitis survivors and mimics motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS), due to its selective impairment, degeneration, or death of motor neurons in the brainstem and spinal cord. Herein, we report a case of PPS in a 68-year-old man with a remote history of bulbar and cervical cord involvement by poliomyelitis, review the relevant literature, and contrast the salient histopathologic features that distinguish our case of PPS from ALS. Full article
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9 pages, 696 KiB  
Article
The Discrepancy and Agreement between Patient-Reported Percentage Pain Reduction and Calculated Percentage Pain Reduction in Chronic Pain Patients
by Adam B. Fink, Charmaine Ong, Moez K. Sumar, Neil C. Patel and Nebojsa Nick Knezevic
Neurol. Int. 2023, 15(2), 560-568; https://doi.org/10.3390/neurolint15020034 - 4 Apr 2023
Cited by 1 | Viewed by 1394
Abstract
Two derivatives of the numeric rating scale (NRS) and visual analog scale (VAS), namely patient-reported percentage pain reduction (PRPPR) and calculated percentage pain reduction (CPPR), are commonly used when evaluating pain reduction. A small number of studies have attempted to assess the agreement [...] Read more.
Two derivatives of the numeric rating scale (NRS) and visual analog scale (VAS), namely patient-reported percentage pain reduction (PRPPR) and calculated percentage pain reduction (CPPR), are commonly used when evaluating pain reduction. A small number of studies have attempted to assess the agreement between PRPPR and CPPR. However, they have been limited in their scope by a focus on specific types of pain, or by their focus on specific treatment modalities. As far as the authors of this article are aware, this is the first study to assess the agreement between PRPPR and CPPR in chronic pain patients, as well as the first to assess how the duration of treatment affects the correlations between PRPPR and CPPR. The aim of this retrospective analysis was to determine whether the duration of treatment affects CPPR and PRPPR, and the discrepancy and agreement between the two. Additionally, the study assessed whether individual treatment modalities, or the lack there of, impacted the discrepancy and correlation between PRPPR and CPPR. The mean PRPPR and CPPR for the entire patient population were 59.98 and 40.71, respectively. The mean discrepancy between the two parameters was 19.27. The agreement between PRPPR and CPPR, as measured by the concordance correlation coefficient, was 0.984 (95% C.I., 0.982–0.986). Full article
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11 pages, 1426 KiB  
Article
Rapid Effects of BCI-Based Attention Training on Functional Brain Connectivity in Poststroke Patients: A Pilot Resting-State fMRI Study
by Larisa Mayorova, Anastasia Kushnir, Viktoria Sorokina, Pranil Pradhan, Margarita Radutnaya, Vasiliy Zhdanov, Marina Petrova and Andrey Grechko
Neurol. Int. 2023, 15(2), 549-559; https://doi.org/10.3390/neurolint15020033 - 27 Mar 2023
Cited by 3 | Viewed by 1916
Abstract
The prevalence of stroke-induced cognitive impairment is high. Effective approaches to the treatment of these cognitive impairments after stroke remain a serious and perhaps underestimated challenge. A BCI-based task-focused training that results in repetitive recruitment of the normal motor or cognitive circuits may [...] Read more.
The prevalence of stroke-induced cognitive impairment is high. Effective approaches to the treatment of these cognitive impairments after stroke remain a serious and perhaps underestimated challenge. A BCI-based task-focused training that results in repetitive recruitment of the normal motor or cognitive circuits may strengthen stroke-affected neuronal connectivity, leading to functional improvements. In the present controlled study, we attempted to evaluate the modulation of neuronal circuits under the influence of 10 days of training in a P3-based BCI speller in subacute ischemic stroke patients. Full article
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