Neurology International

2024

Jump to: 2023, 2022

13 pages, 2343 KiB

Open AccessSystematic Review

Survival After Shunt Therapy in Normal-Pressure Hydrocephalus: A Meta-Analysis of 1614 Patients

by Johannes Wach, Agi Güresir, Erdem Güresir and Martin Vychopen

Neurol. Int. 2024, 16(6), 1438-1450; https://doi.org/10.3390/neurolint16060107 - 11 Nov 2024

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Abstract

Background: Ventriculoperitoneal (VP) shunt therapy is a crucial intervention for normal-pressure hydrocephalus (NPH). This meta-analysis delves into survival time and the impact of baseline symptom burden on survival after VP shunt therapy for NPH, employing reconstructed pooled survival curves and a one-stage meta-analysis. [...] Read more.

Background: Ventriculoperitoneal (VP) shunt therapy is a crucial intervention for normal-pressure hydrocephalus (NPH). This meta-analysis delves into survival time and the impact of baseline symptom burden on survival after VP shunt therapy for NPH, employing reconstructed pooled survival curves and a one-stage meta-analysis. Methods: IPD regarding overall survival (OS) were acquired from published Kaplan–Meier charts, utilizing the R package IPDfromKM in R (Version 4.3.1, the R Foundation for Statistical Computing). Reconstructed Kaplan–Meier charts were then generated from the pooled IPD data. Both one-stage and two-stage meta-analyses were executed, with hazard ratios (HRs) employed as metrics to evaluate effectiveness. Results: From the initial screening of 216 records, five articles encompassing 1614 patients met the eligibility criteria for inclusion. In two of the five included studies, overall survival was stratified by gait score (1–4 vs. ≥4) in 1043 patients, continence score (1–3 vs. ≥4) in 1022 patients, and mRS (0–2 vs. ≥3) in 956 patients. Patients with good gait demonstrated a mean survival of 8.24 years, while those with poor gait had a mean survival of 6.19 years (log-rank test: p < 0.001). The HR for gait was 2.25 (95% CI: 1.81–2.81, p < 0.001). Continence score stratification revealed a significant difference in survival time (log-rank test: p < 0.001), with an HR of 1.66 (95% CI: 1.33–2.06, p < 0.001). Similarly, mRS stratification demonstrated a significant survival difference (log-rank test: p < 0.001), with an HR of 2.21 (95% CI: 1. 74–2.80, p < 0.001). The reconstructed survival curves for all NPH patients treated with VP shunt therapy, pooling data from five studies, revealed a median survival time of 8.82 years (95% CI: 8.23–9.40). Survival rates at 1, 3, 5, 7, 9, 11, and 13 years were 95.7%, 83.8%, 70.5%, 59.5%, 48.7%, 35.8%, and 25.4%, respectively. Comparison with a general control population showed an HR of 1.79 (95% CI: 1.62–1.98, p < 0.001). Conclusions: This comprehensive meta-analysis underscores the influence of baseline symptom burden on survival after VP shunt therapy in NPH. Therapy in the early stages for those without significant comorbidities may enhance survival. Full article

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14 pages, 1364 KiB

Open AccessReview

The Role of Neuropeptide Y in the Pathogenesis of Alzheimer’s Disease: Diagnostic Significance and Neuroprotective Functions

by Ksenia Shapovalova, Yana Zorkina, Olga Abramova, Alisa Andryushchenko, Vladimir Chekhonin and Georgy Kostyuk

Neurol. Int. 2024, 16(6), 1318-1331; https://doi.org/10.3390/neurolint16060100 - 1 Nov 2024

Viewed by 613

Abstract

Background. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. It has been suggested that the factors that cause pathologic changes and lead to the development of AD may also include changes in certain neuropeptides. The implication of the neuropeptide [...] Read more.

Background. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. It has been suggested that the factors that cause pathologic changes and lead to the development of AD may also include changes in certain neuropeptides. The implication of the neuropeptide (NPY) in the pathogenesis of AD and its potential therapeutic role is possible due to the following properties: involvement in adult neurogenesis, regulatory effects on the immune system, the inhibition of potential-dependent Ca²⁺ channels, and the reduction in glutamate excitotoxicity. The aim of our review was to summarize recent data on the role of NPY in AD development and to explore its potential as a biomarker and a possible therapeutic target. Materials and methods. We performed a systematic review of studies, for which we search using the keywords “Alzheimer’s disease and neuropeptide Y”, “Alzheimer’s disease and NPY”, “AD and NPY”, “Neuropeptide Y and Neurodegenerative disease”. Nineteen articles were included in the review. Results. The NPY levels in cerebrospinal fluid and plasma have been found to be reduced or unchanged in AD patients; however, these findings need to be confirmed in more recent studies. Data obtained in transgenic animal models support the role of NPY in AD pathogenesis. The neuroprotective effects of NPY have been demonstrated in vitro and in vivo in AD models. Conclusion. The findings may open new possibilities for using NPY as a diagnostic marker to detect AD at earlier stages of the disease or as a potential therapeutic target due to its neuroprotective properties. Full article

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11 pages, 3056 KiB

Open AccessCase Report

Adult Case of Pontocerebellar Hypoplasia without the Claustrum

by Koji Hayashi, Shiho Mitsuhashi, Ei Kawahara, Asuka Suzuki, Yuka Nakaya, Mamiko Sato and Yasutaka Kobayashi

Neurol. Int. 2024, 16(5), 1132-1142; https://doi.org/10.3390/neurolint16050085 - 7 Oct 2024

Viewed by 877

Abstract

We describe the case of a 63-year-old man with pontocerebellar hypoplasia without the claustrum (CL). The patient had a history of cerebral palsy, intelligent disability, cerebellar atrophy, and seizures since birth. At age 61, brain computed tomography (CT) revealed significant cerebellar and brainstem [...] Read more.

We describe the case of a 63-year-old man with pontocerebellar hypoplasia without the claustrum (CL). The patient had a history of cerebral palsy, intelligent disability, cerebellar atrophy, and seizures since birth. At age 61, brain computed tomography (CT) revealed significant cerebellar and brainstem atrophy. At age 63, he was admitted to our hospital for aspiration pneumonia. Although he was treated with medications, including antibiotics, he died one month after admission. The autopsy revealed a total brain weight of 815 g, with the small-sized frontal lobe, cerebellum, and pons. The cross-section of the fourth ventricle had a slit-like appearance, rather than the typical diamond shape. In addition, bilateral CLs were not observed. Apart from CL, no other missing brain tissue or cells could be identified. Microscopic examinations disclosed neurofibrillary tangles in the hippocampus but not in the cortex; however, neither senile plaques nor Lewy bodies were detected. No acquired lesions, including cerebral infarction, hemorrhage, or necrosis, were noted. We pathologically diagnosed the patient with pontocerebellar hypoplasia without CL. As there have been no prior reports of pontocerebellar hypoplasia lacking CL in adults, this case may represent a new subtype. Congenital CL deficiency is likely associated with abnormalities in brain development. CL may play a role in seizure activity, and the loss of bilateral CLs does not necessarily result in immediate death. Further studies are needed to clarify the functions of CL. Full article

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13 pages, 5853 KiB

Open AccessArticle

HSPB4/CRYAA Protect Photoreceptors during Retinal Detachment in Part through FAIM2 Regulation

by Cagri G. Besirli, Madhu Nath, Jingyu Yao, Mercy Pawar, Angela M. Myers, David Zacks and Patrice E. Fort

Neurol. Int. 2024, 16(5), 905-917; https://doi.org/10.3390/neurolint16050068 - 26 Aug 2024

Viewed by 638

Abstract

Our previous study discussed crystallin family induction in an experimental rat model of retinal detachment. Therefore, we attempted to evaluate the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, as well as its association with the intrinsically neuroprotective [...] Read more.

Our previous study discussed crystallin family induction in an experimental rat model of retinal detachment. Therefore, we attempted to evaluate the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, as well as its association with the intrinsically neuroprotective protein Fas-apoptotic inhibitory molecule 2 (FAIM2). Separation of retina and RPE was induced in rat and mouse eyes by subretinal injection of hyaluronic acid. Retinas were subsequently analyzed for the presence αA-crystallin (HSPB4) and αB-crystallin (HSPB5) proteins using immunohistochemistry and immunoblotting. Photoreceptor death was analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its dependence on its phosphorylation on T148. We further evaluated the interaction between FAIM2 and αA-crystallin using a co-immunoprecipitation assay. Our results showed that α-crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also show that the photoreceptor intrinsically neuroprotective protein FAIM2 is induced and interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is important for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, serving as an important modulator of photoreceptor cell survival under chronic stress conditions. Full article

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12 pages, 1168 KiB

Open AccessArticle

Late-Life Blood Pressure and Cerebral Amyloid Angiopathy: Findings from the U.S. National Alzheimer’s Coordinating Center Uniform Dataset

by Mo-Kyung Sin, N. Maritza Dowling, Jeffrey M. Roseman, Ali Ahmed and Edward Zamrini

Neurol. Int. 2024, 16(4), 821-832; https://doi.org/10.3390/neurolint16040061 - 29 Jul 2024

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Abstract

High blood pressure (BP) and cerebral amyloid angiopathy (CAA) are two common risk factors for intracranial hemorrhage, potentially leading to cognitive impairment. Less is known about the relationship between BP and CAA, the examination of which was the objective of this study. We [...] Read more.

High blood pressure (BP) and cerebral amyloid angiopathy (CAA) are two common risk factors for intracranial hemorrhage, potentially leading to cognitive impairment. Less is known about the relationship between BP and CAA, the examination of which was the objective of this study. We analyzed data from 2510 participants in the National Alzheimer’s Coordinating Center (NACC) who had information on longitudinal BP measurements before death and on CAA from autopsy. Using the average of four systolic BPs (SBPs) prior to death, SBP was categorized into three groups: <120 mmHg (n = 435), 120–139 mmHg (n = 1335), and ≥140 mmHg (n = 740). CAA was diagnosed using immunohistochemistry in 1580 participants and categorized as mild (n = 759), moderate (n = 529), or severe (n = 292). When adjusted for age at death, sex, APOE genotype, Braak, CERAD, antihypertensive medication use, and microinfarcts, the odds ratios (95% CIs) for CAA associated with SBPs of 120–139 and ≥140 mmHg were 0.91 (0.74–1.12) and 1.00 (0.80–1.26), respectively. Findings from predictor effect plots show no variation in the probability of CAA between the three SBP categories. Microbleeds had no association with CAA, but among those with SBP ≥ 130 mmHg, the proportion of those with microbleeds was numerically greater in those with more severe CAA (p for trend, 0.084). In conclusion, we found no evidence of an association between SBP and CAA. Future studies need to develop non-invasive laboratory tests to diagnose CAA and prospectively examine this association and its implication on the pathophysiology and outcome of Alzheimer’s disease. Full article

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16 pages, 690 KiB

Open AccessPerspective

Artificial Intelligence as a Replacement for Animal Experiments in Neurology: Potential, Progress, and Challenges

by Thorsten Rudroff

Neurol. Int. 2024, 16(4), 805-820; https://doi.org/10.3390/neurolint16040060 - 29 Jul 2024

Cited by 1 | Viewed by 3029

Abstract

Animal experimentation has long been a cornerstone of neurology research, but it faces growing scientific, ethical, and economic challenges. Advances in artificial intelligence (AI) are providing new opportunities to replace animal testing with more human-relevant and efficient methods. This article explores the potential [...] Read more.

Animal experimentation has long been a cornerstone of neurology research, but it faces growing scientific, ethical, and economic challenges. Advances in artificial intelligence (AI) are providing new opportunities to replace animal testing with more human-relevant and efficient methods. This article explores the potential of AI technologies such as brain organoids, computational models, and machine learning to revolutionize neurology research and reduce reliance on animal models. These approaches can better recapitulate human brain physiology, predict drug responses, and uncover novel insights into neurological disorders. They also offer faster, cheaper, and more ethical alternatives to animal experiments. Case studies demonstrate AI’s ability to accelerate drug discovery for Alzheimer’s, predict neurotoxicity, personalize treatments for Parkinson’s, and restore movement in paralysis. While challenges remain in validating and integrating these technologies, the scientific, economic, practical, and moral advantages are driving a paradigm shift towards AI-based, animal-free research in neurology. With continued investment and collaboration across sectors, AI promises to accelerate the development of safer and more effective therapies for neurological conditions while significantly reducing animal use. The path forward requires the ongoing development and validation of these technologies, but a future in which they largely replace animal experiments in neurology appears increasingly likely. This transition heralds a new era of more humane, human-relevant, and innovative brain research. Full article

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22 pages, 4437 KiB

Open AccessArticle

Inhibition of Sphingosine Kinase 1 Reduces Sphingosine-1-Phosphate and Exacerbates Amyloid-Beta-Induced Neuronal Cell Death in Mixed-Glial-Cell Culture

by Tomoki Minamihata, Katsura Takano-Kawabe and Mitsuaki Moriyama

Neurol. Int. 2024, 16(4), 709-730; https://doi.org/10.3390/neurolint16040054 - 4 Jul 2024

Viewed by 917

Abstract

In Alzheimer’s disease (AD) pathology, the accumulation of amyloid-beta (Aβ), a main component of senile plaques, activates glial cells and causes neuroinflammation. Excessive neuroinflammation results in neuronal dropouts and finally produces the symptoms of AD. Recent studies suggest that disorder in sphingosine-1-phosphate (S1P) [...] Read more.

In Alzheimer’s disease (AD) pathology, the accumulation of amyloid-beta (Aβ), a main component of senile plaques, activates glial cells and causes neuroinflammation. Excessive neuroinflammation results in neuronal dropouts and finally produces the symptoms of AD. Recent studies suggest that disorder in sphingosine-1-phosphate (S1P) metabolism, especially the decreased expression of sphingosine kinase (SK)1, followed by the reduction in the amount of S1P, can be a promotive factor in AD onset. Thus, we explored the possibility that dysregulated S1P metabolism affects AD through the altered function in glial cells. We evaluated the effect of PF-543, a pharmacological inhibitor of SK1, on the inflammatory responses by lipopolysaccharide (LPS)-activated glial cells, microglia, and astrocytes. The treatment with PF-543 decreased the intracellular S1P content in glial cells. The PF-543 treatment enhanced the nitric oxide (NO) production in the LPS-treated neuron/glia mixed culture. Furthermore, we found that the augmented production of NO and reactive oxygen species (ROS) in the PF-543-treated astrocytes affected the microglial inflammatory responses through humoral factors in the experiment using an astrocyte-conditioned medium. The PF-543 treatment also decreased the microglial Aβ uptake and increased the number of injured neurons in the Aβ-treated neuron/glia mixed culture. These results suggest that a decrease in the glial S1P content can exacerbate neuroinflammation and neurodegeneration through altered glial cell functions. Full article

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Graphical abstract

6 pages, 216 KiB

Open AccessCase Report

Supranuclear Palsy as an Initial Presentation of the Adult-Onset Niemann-Pick Type C

by 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

Cited by 2 | Viewed by 1121

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 [...] Read more.

(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

16 pages, 2738 KiB

Open AccessEditor’s ChoiceReview

Oxidative Stress and Neurodegeneration: Insights and Therapeutic Strategies for Parkinson’s Disease

by 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

Cited by 4 | Viewed by 2474

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 [...] Read more.

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

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2023

Jump to: 2024, 2022

15 pages, 861 KiB

Open AccessReview

Targeting Neutrophil Extracellular Traps for Stroke Prognosis: A Promising Path

by Eirini Liaptsi, Ermis Merkouris, Efthymia Polatidou, Dimitrios Tsiptsios, Aimilios Gkantzios, Christos Kokkotis, Foivos Petridis, Foteini Christidi, Stella Karatzetzou, Christos Karaoglanis, Anna-Maria Tsagkalidi, Nikolaos Chouliaras, Konstantinos Tsamakis, Maria Protopapa, Dimitrios Pantazis-Pergaminelis, Panagiotis Skendros, Nikolaos Aggelousis and Konstantinos Vadikolias

Neurol. Int. 2023, 15(4), 1212-1226; https://doi.org/10.3390/neurolint15040076 - 28 Sep 2023

Cited by 5 | Viewed by 2071

Abstract

Stroke has become the first cause of functional disability and one of the leading causes of mortality worldwide. Therefore, it is of crucial importance to develop accurate biomarkers to assess stroke risk and prognosis. Emerging evidence suggests that neutrophil extracellular trap (NET) levels [...] Read more.

Stroke has become the first cause of functional disability and one of the leading causes of mortality worldwide. Therefore, it is of crucial importance to develop accurate biomarkers to assess stroke risk and prognosis. Emerging evidence suggests that neutrophil extracellular trap (NET) levels may serve as a valuable biomarker to predict stroke occurrence and functional outcome. NETs are known to create a procoagulant state by serving as a scaffold for tissue factor (TF) and platelets inducing thrombosis by activating coagulation pathways and endothelium. A literature search was conducted in two databases (MEDLINE and Scopus) to trace all relevant studies published between 1 January 2016 and 31 December 2022, addressing the potential utility of NETs as a stroke biomarker. Only full-text articles in English were included. The current review includes thirty-three papers. Elevated NET levels in plasma and thrombi seem to be associated with increased mortality and worse functional outcomes in stroke, with all acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage included. Additionally, higher NET levels seem to correlate with worse outcomes after recanalization therapies and are more frequently found in strokes of cardioembolic or cryptogenic origin. Additionally, total neutrophil count in plasma seems also to correlate with stroke severity. Overall, NETs may be a promising predictive tool to assess stroke severity, functional outcome, and response to recanalization therapies. Full article

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11 pages, 1194 KiB

Open AccessArticle

A Comparative Analysis of Symmetry Indices for Spatiotemporal Gait Features in Early Parkinson’s Disease

by Erasmia Giannakou, Styliani Fotiadou, Vassilios Gourgoulis, Georgios Mavrommatis and Nikolaos Aggelousis

Neurol. Int. 2023, 15(3), 1129-1139; https://doi.org/10.3390/neurolint15030070 - 7 Sep 2023

Viewed by 1505

Abstract

This study compared the five most commonly used equations for calculating gait symmetry in discrete variables among Parkinson’s disease patients. Twelve patients (five women and seven men) performed ten consecutive gait trials on a 10 m walkway. Gait data were collected using eight [...] Read more.

This study compared the five most commonly used equations for calculating gait symmetry in discrete variables among Parkinson’s disease patients. Twelve patients (five women and seven men) performed ten consecutive gait trials on a 10 m walkway. Gait data were collected using eight optoelectronic cameras (100 fr/s). The analysis focused on various spatiotemporal parameters, including cadence, step time, stride time, single support, double support, walking speed, step length, stride length, step width, and foot angle. Five symmetry indices were calculated for each trial rather than averaging the ten recorded trials. The variability in and reliability of each symmetry equation were assessed using the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. Additionally, Bland–Altman plots were produced to visualize the agreement between each pair of methods for each spatiotemporal parameter. The results revealed that the symmetry ratio method exhibited lower variability and higher reliability compared with the other four indices across all spatiotemporal gait parameters. However, it was found that the reliability of a single trial was generally poor, regardless of the symmetry calculation formula used. Therefore, we recommend basing measurements of gait asymmetry in Parkinson’s disease on multiple trials. Full article

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8 pages, 2704 KiB

Open AccessBrief Report

Serum GDF-15 Levels in Patients with Parkinson’s Disease, Progressive Supranuclear Palsy, and Multiple System Atrophy

by Noriyuki Miyaue, Hayato Yabe and Masahiro Nagai

Neurol. Int. 2023, 15(3), 1044-1051; https://doi.org/10.3390/neurolint15030066 - 30 Aug 2023

Viewed by 1423

Abstract

Serum growth differentiation factor 15 (GDF-15) levels are elevated in patients with Parkinson’s disease (PD) and may help differentiate these patients from healthy individuals. We aimed to clarify whether serum GDF-15 levels can help differentiate PD from atypical parkinsonian syndromes and determine the [...] Read more.

Serum growth differentiation factor 15 (GDF-15) levels are elevated in patients with Parkinson’s disease (PD) and may help differentiate these patients from healthy individuals. We aimed to clarify whether serum GDF-15 levels can help differentiate PD from atypical parkinsonian syndromes and determine the association between serum GDF-15 levels and clinical parameters. We prospectively enrolled 46, 15, and 12 patients with PD, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA), respectively. The serum GDF-15 level in patients with PD (1394.67 ± 558.46 pg/mL) did not differ significantly from that in patients with PSP (1491.27 ± 620.78 pg/mL; p = 0.573) but was significantly higher than that in patients with MSA (978.42 ± 334.66 pg/mL; p = 0.017). Serum GDF-15 levels were positively correlated with age in patients with PD (r = 0.458; p = 0.001); PSP (r = 0.565; p = 0.028); and MSA (r = 0.708; p = 0.010). After accounting for age differences, serum GDF-15 levels did not differ significantly between patients with PD and MSA (p = 0.114). Thus, age has a strong influence on serum GDF-15 levels, which may not differ significantly between patients with PD and atypical parkinsonian syndromes such as PSP and MSA. Full article

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13 pages, 870 KiB

Open AccessReview

In Search of a Function for the N6-Methyladenosine in Epitranscriptome, Autophagy and Neurodegenerative Diseases

by Naoko Suga, Yuka Ikeda, Sayuri Yoshikawa, Kurumi Taniguchi, Haruka Sawamura and Satoru Matsuda

Neurol. Int. 2023, 15(3), 967-979; https://doi.org/10.3390/neurolint15030062 - 10 Aug 2023

Cited by 4 | Viewed by 2838

Abstract

Changes in epitranscriptome with N6-methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. [...] Read more.

Changes in epitranscriptome with N6-methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. Importantly, the m6A methylation may be associated with various neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, aging-related diseases, and/or aging itself. In addition, the m6A methylation might functionally regulate the eukaryotic transcriptome by influencing the splicing, export, subcellular localization, translation, stability, and decay of mRNAs. Neurodegenerative diseases may possess a wide variety of phenotypes, depending on the neurons that degenerate on occasion. Interestingly, an increasing amount of evidence has indicated that m6A modification could modulate the expression of autophagy-related genes and promote autophagy in neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) could stimulate the m6A RNA methylation, which may also be related to the regulation of autophagy and/or the development of neurodegenerative diseases. Both m6A modification and autophagy could also play critical roles in regulating the health condition of neurons. Therefore, a comprehensive understanding of the m6A and autophagy relationship in human diseases may benefit in developing therapeutic strategies in the future. This paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of neurodegenerative diseases and/or aging, discussing the possible therapeutic procedures related to mechanisms of m6A RNA methylation and autophagy. Full article

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13 pages, 2841 KiB

Open AccessArticle

Modified TPP-MoS₂ QD Blend as a Bio-Functional Model for Normalizing Microglial Dysfunction in Alzheimer’s Disease

by Ohoud A. Alomari, Safaa Qusti, Maha Balgoon, Fadwa Aljoud, Khalid A. Alamry and Mahmoud A. Hussein

Neurol. Int. 2023, 15(3), 954-966; https://doi.org/10.3390/neurolint15030061 - 8 Aug 2023

Cited by 3 | Viewed by 1966

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of β-amyloid peptide (Aβ) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play [...] Read more.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of β-amyloid peptide (Aβ) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play an important role in maintaining brain homeostasis through a variety of phenotypes, including the pro-inflammatory phenotype and anti-inflammatory phenotypes. However, persistently activated microglial cells generate reactive species and neurotoxic mediators. Therefore, inhibitors of microglial activation are seen to have promise in AD control. The modified TPP/MoS₂ QD blend is a mitochondrion-targeted nanomaterial that exhibits cytoprotective activities and antioxidant properties through scavenging free radicals. In the present study, the cell viability and cytotoxicity of the DSPE-PEG-TPP/MoS₂ QD blend on microglial cells stimulated by Aβ were investigated. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also assessed. In addition, pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), transforming growth factor beta (TGF-β), inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-I) were measured in the presence or absence of the DSPE-PEG-TPP/MoS₂ QD blend on an immortalized microglia cells activated by accumulation of Aβ. We found that the DSPE-PEG-TPP/MoS₂ QD blend was biocompatible and nontoxic at specific concentrations. Furthermore, the modified TPP/MoS₂ QD blend significantly reduced the release of free radicals and improved the mitochondrial function through the upregulation of MMP in a dose-dependent manner on microglial cells treated with Aβ. In addition, pre-treatment of microglia with the DSPE-PEG-TPP/MoS₂ QD blend at concentrations of 25 and 50 μg/mL prior to Aβ stimulation significantly inhibited the release and expression of pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, and iNOS. Nevertheless, the anti-inflammatory cytokines TGF-β and Arg-I were activated. These findings suggest that the modified TPP/MoS₂ QD blend reduced oxidative stress, inflammation and improved the mitochondrial function in the immortalized microglial cells (IMG) activated by Aβ. Overall, our research shows that the DSPE-PEG-TPP/MoS₂ QD blend has therapeutic promise for managing AD and can impact microglia polarization. Full article

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10 pages, 287 KiB

Open AccessEditor’s ChoiceReview

Ketamine Evolving Clinical Roles and Potential Effects with Cognitive, Motor and Driving Ability

by Amber N. Edinoff, Saveen Sall, Colby B. Koontz, Ajah K. Williams, DeMarcus Drumgo, Aya Mouhaffel, Elyse M. Cornett, Kevin S. Murnane and Alan D. Kaye

Neurol. Int. 2023, 15(1), 352-361; https://doi.org/10.3390/neurolint15010023 - 3 Mar 2023

Viewed by 2481

Abstract

While driving under the influence of drugs, drivers are more likely to be involved in and cause more accidents than drivers who do not drive under the influence. Ketamine is derived from phencyclidine and acts as a noncompetitive antagonist and allosteric modulator of [...] Read more.

While driving under the influence of drugs, drivers are more likely to be involved in and cause more accidents than drivers who do not drive under the influence. Ketamine is derived from phencyclidine and acts as a noncompetitive antagonist and allosteric modulator of N-methyl-D-aspartate receptors. Ketamine has been used to treat a variety of psychiatric disorders, with the most notable being treatment-resistant depression. With the rise of at-home ketamine treatment companies, the safety of unsupervised administration remains under evaluation. A study with ketamine and a ketamine-like medication, rapasitnel, showed that those who were given ketamine experienced more sleepiness and had decreased self-reported motivation and confidence in their driving abilities. Moreover, there seem to be significant differences in the acute versus persistent effects of ketamine, as well as the anesthetic versus subanesthetic doses, both in terms of effects and outcomes. These divergent effects complicate the clinical uses of ketamine, specifically involving driving, drowsiness, and cognitive abilities. This review aims to describe not only the various clinical uses of ketamine but also the potentially detrimental effects of driving under the influence, which should be understood to help with counseling the patients who use these substances, both for their well-being and to protect public safety. Full article

14 pages, 310 KiB

Open AccessReview

Transcranial Stimulation for the Treatment of Stimulant Use Disorder

by Amber N. Edinoff, Saveen Sall, T. Dean Roberts, Henry H. Tomlinson, Lenise G. Soileau III, Eric D. Jackson, Kevin S. Murnane, Danielle M. Wenger, Elyse M. Cornett, Jaime Toms, Deepak Kumbhare, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2023, 15(1), 325-338; https://doi.org/10.3390/neurolint15010021 - 27 Feb 2023

Cited by 2 | Viewed by 3048

Abstract

The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. Furthermore, approximately one of every four MIs is cocaine-induced [...] Read more.

The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. Furthermore, approximately one of every four MIs is cocaine-induced among patients aged 18 to 45. Methamphetamine use has been associated with nerve terminal damage in the dopaminergic system resulting in impaired motor function, cognitive decline, and co-morbid psychiatric disorders. Current treatment options for StUD are extremely limited, and there are currently no FDA-approved pharmacotherapies. Behavioral interventions are considered first-line treatment; however, in a recent meta-analysis comparing behavioral treatment options for cocaine, contingency management programs provided the only significant reduction in use. Current evidence points to the potential of various neuromodulation techniques as the next best modality in treating StUD. The most promising evidence thus far has been transcranial magnetic stimulation which several studies have shown to reduce risk factors associated with relapse. Another more invasive neuromodulation technique being studied is deep-brain stimulation, which has shown promising results in its ability to modulate reward circuits to treat addiction. Results showing the impact of transcranial magnetic stimulation (TMS) in the treatment of StUD are limited by the lack of studies conducted and the limited understanding of the neurological involvement driving addiction-based diseases such as StUD. Future studies should seek to provide data on consumption-reducing effects rather than craving evaluations. Full article

16 pages, 1771 KiB

Open AccessReview

Preclinical Research on Focused Ultrasound-Mediated Blood–Brain Barrier Opening for Neurological Disorders: A Review

by Chanho Kong and Won Seok Chang

Neurol. Int. 2023, 15(1), 285-300; https://doi.org/10.3390/neurolint15010018 - 14 Feb 2023

Cited by 9 | Viewed by 3795

Abstract

Several therapeutic agents for neurological disorders are usually not delivered to the brain owing to the presence of the blood–brain barrier (BBB), a special structure present in the central nervous system (CNS). Focused ultrasound (FUS) combined with microbubbles can reversibly and temporarily open [...] Read more.

Several therapeutic agents for neurological disorders are usually not delivered to the brain owing to the presence of the blood–brain barrier (BBB), a special structure present in the central nervous system (CNS). Focused ultrasound (FUS) combined with microbubbles can reversibly and temporarily open the BBB, enabling the application of various therapeutic agents in patients with neurological disorders. In the past 20 years, many preclinical studies on drug delivery through FUS-mediated BBB opening have been conducted, and the use of this method in clinical applications has recently gained popularity. As the clinical application of FUS-mediated BBB opening expands, it is crucial to understand the molecular and cellular effects of FUS-induced microenvironmental changes in the brain so that the efficacy of treatment can be ensured, and new treatment strategies established. This review describes the latest research trends in FUS-mediated BBB opening, including the biological effects and applications in representative neurological disorders, and suggests future directions. Full article

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12 pages, 1127 KiB

Open AccessArticle

Migraine Disability Improvement during Treatment with Galcanezumab in Patients with Chronic and High Frequency Episodic Migraine

by Francesca Schiano di Cola, Marco Bolchini, Salvatore Caratozzolo, Giulia Ceccardi, Matteo Cortinovis, Paolo Liberini, Renata Rao and Alessandro Padovani

Neurol. Int. 2023, 15(1), 273-284; https://doi.org/10.3390/neurolint15010017 - 13 Feb 2023

Cited by 5 | Viewed by 2090

Abstract

Background: The aim of the present study was to assess the migraine outcome, in particular migraine disability, in chronic (CM) and high frequency episodic migraine (HFEM) patients in treatment with galcanezumab. Methods: The present study was conducted at the Headache Centre of Spedali [...] Read more.

Background: The aim of the present study was to assess the migraine outcome, in particular migraine disability, in chronic (CM) and high frequency episodic migraine (HFEM) patients in treatment with galcanezumab. Methods: The present study was conducted at the Headache Centre of Spedali Civili of Brescia. Patients were treated with galcanezumab 120 mg monthly. Clinical and demographical information were collected at the baseline (T0). Data about outcome, analgesics consumption and disability (MIDAS and HIT-6 scores) were collected quarterly. Results: Fifty-four consecutive patients were enrolled. Thirty-seven patients had a diagnosis of CM, 17 of HFEM. During treatment, patients reported a significant reduction in terms of mean headache/migraine days (p < 0.001), the attacks’ pain intensity (p = 0.001) and monthly consumed analgesics (p < 0.001). The MIDAS and HIT-6 scores also documented a significant improvement (p < 0.001). At the baseline, all patients documented a severe degree of disability (MIDAS score ≥ 21). Following six months of treatment, only 29.2% of patients still documented a MIDAS score ≥ 21, with one third of patients documenting little or no disability. A > 50% MIDAS reduction, compared to baseline, was observed in up to 94.6% of patients, following the first three months of treatment. A similar outcome was found for HIT-6 scores. A significant positive correlation was found between headache days and MIDAS at T3 and T6 (T6 > T3), but not baseline. Discussion: Monthly prophylactic treatment with galcanezumab was found to be effective in both CM and HFEM, especially in reducing migraine burden and disability. Full article

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26 pages, 419 KiB

Open AccessReview

Thwarting Alzheimer’s Disease through Healthy Lifestyle Habits: Hope for the Future

by Vijaya Laxmi Govindugari, Sowmya Golla, S. Deepak Mohan Reddy, Alisha Chunduri, Lakshmayya S. V. Nunna, Jahanavi Madasu, Vishwanutha Shamshabad, Mounica Bandela and Vidyani Suryadevara

Neurol. Int. 2023, 15(1), 162-187; https://doi.org/10.3390/neurolint15010013 - 28 Jan 2023

Cited by 7 | Viewed by 4076

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that slowly disintegrates memory and thinking skills. Age is known to be the major risk factor in AD, but there are several nonmodifiable and modifiable causes. The nonmodifiable risk factors such as family history, high cholesterol, [...] Read more.

Alzheimer’s disease (AD) is a neurodegenerative disorder that slowly disintegrates memory and thinking skills. Age is known to be the major risk factor in AD, but there are several nonmodifiable and modifiable causes. The nonmodifiable risk factors such as family history, high cholesterol, head injuries, gender, pollution, and genetic aberrations are reported to expediate disease progression. The modifiable risk factors of AD that may help prevent or delay the onset of AD in liable people, which this review focuses on, includes lifestyle, diet, substance use, lack of physical and mental activity, social life, sleep, among other causes. We also discuss how mitigating underlying conditions such as hearing loss and cardiovascular complications could be beneficial in preventing cognitive decline. As the current medications can only treat the manifestations of AD and not the underlying process, healthy lifestyle choices associated with modifiable factors is the best alternative strategy to combat the disease. Full article

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22 pages, 735 KiB

Open AccessReview

Narrative Review Concerning the Clinical Spectrum of Ophthalmological Impairments in Parkinson’s Disease

by Alina Zorina Stuparu, Sanda Jurja, Alexandru Floris Stuparu and Any Axelerad

Neurol. Int. 2023, 15(1), 140-161; https://doi.org/10.3390/neurolint15010012 - 26 Jan 2023

Cited by 2 | Viewed by 2244

Abstract

Ophthalmic non-motor impairments are common in Parkinson’s disease patients, from the onset of the neurodegenerative disease and even prior to the development of motor symptoms. This is a very crucial component of the potential for early detection of this disease, even in its [...] Read more.

Ophthalmic non-motor impairments are common in Parkinson’s disease patients, from the onset of the neurodegenerative disease and even prior to the development of motor symptoms. This is a very crucial component of the potential for early detection of this disease, even in its earliest stages. Since the ophthalmological disease is extensive and impacts all extraocular and intraocular components of the optical analyzer, a competent assessment of it would be beneficial for the patients. Because the retina is an extension of the nervous system and has the same embryonic genesis as the central nervous system, it is helpful to investigate the retinal changes in Parkinson’s disease in order to hypothesize insights that may also be applicable to the brain. As a consequence, the detection of these symptoms and signs may improve the medical evaluation of PD and predict the illness’ prognosis. Another valuable aspect of this pathology is the fact that the ophthalmological damage contributes significantly to the decrease in the quality of life of patients with Parkinson’s disease. We provide an overview of the most significant ophthalmologic impairments associated with Parkinson’s disease. These results certainly constitute a large number of the prevalent visual impairments experienced by PD patients. Full article

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21 pages, 5956 KiB

Open AccessEditor’s ChoiceArticle

Inflammation and Treatment-Resistant Depression from Clinical to Animal Study: A Possible Link?

by Lara F. Almutabagani, Raghad A. Almanqour, Jawza F. Alsabhan, Abdulaziz M. Alhossan, Maha A. Alamin, Haya M. Alrajeh, Asma S. Alonazi, Ahmed M. El-Malky and Nouf M. Alrasheed

Neurol. Int. 2023, 15(1), 100-120; https://doi.org/10.3390/neurolint15010009 - 16 Jan 2023

Cited by 11 | Viewed by 2947

Abstract

The aim of this study was to investigate the relationship between treatment-resistant depression (TRD) and inflammation in humans and experimental models. For the human study, a retrospective cohort study was conducted with 206 participants; half were on antidepressants for major depressive disorder. The [...] Read more.

The aim of this study was to investigate the relationship between treatment-resistant depression (TRD) and inflammation in humans and experimental models. For the human study, a retrospective cohort study was conducted with 206 participants; half were on antidepressants for major depressive disorder. The patients were divided into healthy and depressed groups. Inflammation was assessed based on the values of the main inflammatory biomarkers (CRP, WBC and ESR). For the animal experiments, 35 adult male Wistar rats were assigned to stressed and non-stressed groups. Inflammation and stress were induced using lipopolysaccharide and chronic unpredictable mild stress. A 10 mg/kg intraperitoneal injection of fluoxetine (FLX), a known antidepressant, was simultaneously administered daily for 4 weeks. Behavioral tests were performed. The plasma levels of inflammatory and stress biomarkers were measured and were significantly higher in the stressed and non-responsive groups in both studies. This study provides evidence of the link between inflammation and TRD. We further observed a possible link via the Phosphorylated Janus Kinase 2 and Phosphorylated Signal Transducer and Activator of Transcription 3 (P-JAK2/P-STAT3) signaling pathway and found that chronic stress and high inflammation hinder the antidepressant effects of FLX. Thus, non-response to antidepressants could be mitigated by treating inflammation to improve the antidepressant effect in patients with TRD. Full article

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2022

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12 pages, 288 KiB

Open AccessReview

Cognitive Rehabilitation in Schizophrenia-Associated Cognitive Impairment: A Review

by Elli Zoupa, Olympia Bogiatzidou, Vasileios Siokas, Ioannis Liampas, Georgios Tzeferakos, Venetsanos Mavreas, Stelios Stylianidis and Efthimios Dardiotis

Neurol. Int. 2023, 15(1), 12-23; https://doi.org/10.3390/neurolint15010002 - 29 Dec 2022

Cited by 3 | Viewed by 2943

Abstract

Patients suffering from schizophrenia often experience cognitive disturbances. Cognitive rehabilitation—computerized or non-computerized—is widely known as an alternative way to enhance cognitive functioning in patients with schizophrenia. The aim of the present review was to examine the role of cognitive rehabilitation (both computerized and [...] Read more.

Patients suffering from schizophrenia often experience cognitive disturbances. Cognitive rehabilitation—computerized or non-computerized—is widely known as an alternative way to enhance cognitive functioning in patients with schizophrenia. The aim of the present review was to examine the role of cognitive rehabilitation (both computerized and non-computerized) for the alleviation of cognitive impairment in schizophrenia patients. Fourteen relative studies were examined and included in the present review. The results revealed that both computerized and non-computerized cognitive rehabilitation could enhance cognitive functioning and more specifically memory, attention, executive functioning, processing speed and in a few cases, even non-cognitive impairments, such as other schizophrenia symptoms. The present results support the efficacy of cognitive rehabilitation in schizophrenia patients, regardless of whether it is computerized or non-computerized. As the randomized control trials (RCTs) are limited in number, there is urgent need for more RCTs and longitudinal studies combining different kinds of interventions, as well as systematic reviews and meta-analyses, in order to further investigate and confirm the current results. Full article

6 pages, 1007 KiB

Open AccessCase Report

Anti-MOG Positive Bilateral Optic Neuritis and Brainstem Encephalitis Secondary to COVID-19 Infection: A Case Report

by Zisis Tsouris, Antonios Provatas, Christos Bakirtzis, Athina-Maria Aloizou, Vasileios Siokas, Vana Tsimourtou, Nikolaos Grigoriadis, Georgios M. Hadjigeorgiou and Efthimios Dardiotis

Neurol. Int. 2022, 14(4), 991-996; https://doi.org/10.3390/neurolint14040078 - 30 Nov 2022

Cited by 5 | Viewed by 2529

Abstract

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation [...] Read more.

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation of anti-MOG positive optic neuritis as well as anti-MOG positive encephalitis after COVID-19 infection. (2) Case Report: A 59-year-old female patient, with a recent history of COVID-19 infection, presented a progressive reduction of visual acuity and bilateral retrobulbar pain for the last 20 days. An ophthalmological examination revealed a decreased visual acuity (counting fingers) and a bilateral papilledema. An MRI scan of the brain revealed a mild thickening of the bilateral optic nerves and high-intensity lesions in the medial and right lateral pons. A high titer of IgG and IgM antibodies against SARS-CoV-2 in serum and antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) in serum and CSF were revealed. The diagnosis of anti-MOG brainstem encephalitis and optic neuritis was set. (3) Conclusions: The history of COVID-19 infection should raise awareness about these autoimmune and infection-triggered diseases, such as anti-MOG antibody disease. Full article

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10 pages, 1675 KiB

Open AccessReview

Lights on for Autism: Exploring Photobiomodulation as an Effective Therapeutic Option

by Catherine Hamilton, Ann Liebert, Vincent Pang, Pierre Magistretti and John Mitrofanis

Neurol. Int. 2022, 14(4), 884-893; https://doi.org/10.3390/neurolint14040071 - 27 Oct 2022

Cited by 6 | Viewed by 8483

Abstract

Autism is a neurodevelopmental condition that starts in childhood and continues into adulthood. The core characteristics include difficulties with social interaction and communication, together with restricted and repetitive behaviours. There are a number of key abnormalities of brain structure and function that trigger [...] Read more.

Autism is a neurodevelopmental condition that starts in childhood and continues into adulthood. The core characteristics include difficulties with social interaction and communication, together with restricted and repetitive behaviours. There are a number of key abnormalities of brain structure and function that trigger these behavioural patterns, including an imbalance of functional connectivity and synaptic transmission, neuronal death, gliosis and inflammation. In addition, autism has been linked to alterations in the gut microbiome. Unfortunately, as it stands, there are few treatment options available for patients. In this mini-review, we consider the effectiveness of a potential new treatment for autism, known as photobiomodulation, the therapeutic use of red to near infrared light on body tissues. This treatment has been shown in a range of pathological conditions-to improve the key changes that characterise autism, including the functional connectivity and survival patterns of neurones, the patterns of gliosis and inflammation and the composition of the microbiome. We highlight the idea that photobiomodulation may form an ideal treatment option for autism, one that is certainly worthy of further investigation. Full article

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11 pages, 1189 KiB

Open AccessSystematic Review

Erdheim–Chester Disease with Isolated CNS Involvement: A Systematic Review of the Literature

by Anam Haque, Carlos A. Pérez, Thejasvi A. Reddy and Rajesh K. Gupta

Neurol. Int. 2022, 14(3), 716-726; https://doi.org/10.3390/neurolint14030060 - 5 Sep 2022

Cited by 7 | Viewed by 2766

Abstract

Erdheim–Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes [...] Read more.

Erdheim–Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes in published ECD patients presenting with neurological symptoms. A PubMed literature search was conducted for articles (published between January 1980 and June 2021) on ECD cases presenting with neurological manifestations. We analyzed the data of 40 patients, including our patient. Cranial neuropathies and ataxia were the most frequent clinical manifestations. A total of 50% of the symptomatic ECD CNS lesions were intraparenchymal and nearly 33% of patients died due to the disease itself or complications. CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes. Full article

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5 pages, 1191 KiB

Open AccessCase Report

A Patient with Erdheim-Chester Disease Limited to Central Nervous System

by Rajesh K. Gupta, Anam Haque, Thejasvi A. Reddy and Carlos A. Pérez

Neurol. Int. 2022, 14(3), 678-682; https://doi.org/10.3390/neurolint14030056 - 26 Aug 2022

Cited by 2 | Viewed by 2169

Abstract

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis, a multisystem disorder, which has higher mortality when presented with CNS involvement. We report a 46-year-old woman who has ECD with exclusive CNS involvement. She presented with intracranial hemorrhage and had a poor [...] Read more.

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis, a multisystem disorder, which has higher mortality when presented with CNS involvement. We report a 46-year-old woman who has ECD with exclusive CNS involvement. She presented with intracranial hemorrhage and had a poor response to corticosteroid and interferon. She required multiple debulking procedures and eventually responded well to cobimetinib. She has not had any other organ involvement thus far. This report highlights that CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes. Full article

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10 pages, 1785 KiB

Open AccessCase Report

Relevance of Medullary Vein Sign in Neurosarcoidosis

by Richard Liberio, Emily Kramer, Anza B. Memon, Ryan Reinbeau, Parissa Feizi, Joe Joseph, Janet Wu and Shitiz Sriwastava

Neurol. Int. 2022, 14(3), 638-647; https://doi.org/10.3390/neurolint14030052 - 14 Aug 2022

Cited by 3 | Viewed by 2637

Abstract

Background: Central nervous system involvement is uncommon in patients with sarcoidosis. It remains a diagnostic challenge for clinicians, as there is a broad differential diagnosis that matches the presenting neurological signs. Often, the imaging findings also overlap with other disease entities. One understudied [...] Read more.

Background: Central nervous system involvement is uncommon in patients with sarcoidosis. It remains a diagnostic challenge for clinicians, as there is a broad differential diagnosis that matches the presenting neurological signs. Often, the imaging findings also overlap with other disease entities. One understudied finding in patients with neurosarcoidosis is the presence of medullary vein engorgement on SWI imaging, termed the “medullary vein sign”, which has been postulated to be a specific sign for neurosarcoidosis. This study aims to provide an understanding of the diagnostic potential of the medullary vein sign. Methods: Thirty-two patients who presented with neurologic signs concerning for possible neurosarcoidosis were analyzed retrospectively for the presence of the medullary vein sign. Results: Out of these cases, 7 cases of definitive neurosarcoidosis cases were found based on other imaging signs, biopsy and CSF analysis; the remaining were classified into groups as possible (16), probable (5) and (4) cases of other infectious meningoencephalitis including 2 cases of autoimmune encephalitis. Seven patients among all of these cases were found to have the medullary vein sign on imaging, with five cases with confirmed and two cases from possible neurosarcoidosis. The sensitivity of the medullary vein sign in this study was 71.4%, and the specificity was 92.3%. Discussion: The benefits of improving diagnostic criteria for neurosarcoidosis include more rapid diagnosis leading to more prompt treatment, less exposure to potentially harmful antibiotics or antifungals, and less long-term neurological effects. Our results support that the medullary vein sign will potentially fill in the diagnostic gaps that have challenged the timely diagnosis of neurosarcoidosis. Conclusions: Our findings support that the medullary vein sign has a high specificity and should be included in the diagnostic criteria for neurosarcoidosis. Full article

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10 pages, 288 KiB

Open AccessBrief Report

Self-Awareness of Cognitive Efficiency, Cognitive Status, Insight, and Financial Capacity in Patients with Mild AD, aMCI, and Healthy Controls: An Intriguing Liaison with Clinical Implications?

by Vaitsa Giannouli and Magdalini Tsolaki

Neurol. Int. 2022, 14(3), 628-637; https://doi.org/10.3390/neurolint14030051 - 30 Jul 2022

Cited by 8 | Viewed by 2454

Abstract

Objectives: This study compares objective measures of cognitive performance with subjective perception of specific performance on neuropsychological tests examining basic cognitive domains, including, for the first time, financial capacity. Additionally, differences in assessment between single- and multiple-domain aMCI, mild AD, and healthy elderly [...] Read more.

Objectives: This study compares objective measures of cognitive performance with subjective perception of specific performance on neuropsychological tests examining basic cognitive domains, including, for the first time, financial capacity. Additionally, differences in assessment between single- and multiple-domain aMCI, mild AD, and healthy elderly regarding insight are examined. Methods: Participants completed a number of neuropsychological tests and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). After every test, participants were asked to complete the Clinical Insight Rating scale (CIR) and to self-evaluate their performance by comparing it to what they considered as average for people of their age and educational level. Results: These preliminary findings show significant differences in the self-assessment patterns of the four groups in measures of verbal memory, visuospatial perception and memory, executive functions, tests of attention, and financial capacity. Mild AD expressed the highest overestimations, followed by single- and multiple-domain aMCI as well as controls. Accuracy of self-report is not uniform across groups and functional areas. Conclusions: Unawareness of memory deficits in both MCI subtypes is contradictory to subjective memory complaints as being an important component for clinical diagnosis. Financial capacity is overestimated in MCI and mild AD, a finding that has a plethora of clinical and legal implications. Full article

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11 pages, 465 KiB

Open AccessArticle

Diagnostic Accuracy of the Five-Word Test for Mild Cognitive Impairment Due to Alzheimer’s Disease

by Chiara Fornari, Francesco Mori, Nicola Zoppi, Ilenia Libri, Chiara Silvestri, Maura Cosseddu, Rosanna Turrone, Matteo Maffi, Salvatore Caratozzolo, Barbara Borroni, Alessandro Padovani and Alberto Benussi

Neurol. Int. 2022, 14(2), 357-367; https://doi.org/10.3390/neurolint14020029 - 6 Apr 2022

Cited by 5 | Viewed by 3070

Abstract

New diagnostic methods have been developed for the early diagnosis of Alzheimer’s disease (AD) with the primary purpose of intercepting the transition-phase (mild cognitive impairment, MCI) between normal aging and dementia. We aimed to explore whether the five-word test (FWT) and the mini-mental [...] Read more.

New diagnostic methods have been developed for the early diagnosis of Alzheimer’s disease (AD) with the primary purpose of intercepting the transition-phase (mild cognitive impairment, MCI) between normal aging and dementia. We aimed to explore whether the five-word test (FWT) and the mini-mental state examination (MMSE) are predictive for the early diagnosis of MCI due to AD (AD-MCI). We computed ROC analyses to evaluate the sensitivity and specificity of MMSE and FWT in predicting abnormal CSF (t-Tau, p-Tau₁₈₁, Aβ_1–42) and amyloid-PET biomarkers. AD-MCI patients showed lower MMSE and FWT scores (all p < 0.001) than non-AD-MCI. The best predictor of amyloid plaques’ presence at amyloid-PET imaging was the encoding sub-score of the FWT (AUC = 0.84). Both FWT and MMSE had low/moderate accuracy for the detection of pathological CSF Aβ₄₂, t-Tau and p-Tau₁₈₁ values, with higher accuracy for the t-Tau/Aβ_1–42 ratio. In conclusion, the FWT, as a single-domain cognitive screening test, seems to be prompt and moderately accurate tool for the identification of an underlying AD neuropathological process in patients with MCI, supporting the importance of associating biomarkers evaluation in the work-up of patients with dementing neurodegenerative disorders. Full article

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1 pages, 169 KiB

Open AccessEditorial

Advances in Neurodegenerative Diseases

by Vasileios Siokas and Efthimios Dardiotis

Neurol. Int. 2022, 14(2), 336; https://doi.org/10.3390/neurolint14020027 - 28 Mar 2022

Viewed by 1910

Abstract

A multitude of diseases presenting a wide variety of phenotypic appearances are included in neurodegenerative disorders [...] Full article

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