Neurology International

24 pages, 4371 KiB

Open AccessArticle

Novel Gene-Informed Regional Brain Targets for Clinical Screening for Major Depression

by G. Lorenzo Odierna, Christopher F. Sharpley, Vicki Bitsika, Ian D. Evans and Kirstan A. Vessey

Neurol. Int. 2025, 17(6), 96; https://doi.org/10.3390/neurolint17060096 - 19 Jun 2025

Viewed by 554

Background/Objectives: Major Depression (MD) is a common disorder that has significant social and economic impacts. Approximately 30% of all MD patients are refractory to common treatments, representing a major obstacle to managing the impacts of depression. One potential explanation for the incomplete treatment [...] Read more.

Background/Objectives: Major Depression (MD) is a common disorder that has significant social and economic impacts. Approximately 30% of all MD patients are refractory to common treatments, representing a major obstacle to managing the impacts of depression. One potential explanation for the incomplete treatment efficacy in MD is a substantial divergence in the mechanisms and brain networks involved in different subtypes of the disorder. The aim of this study was to identify novel brain regional targets for MD clinical screening using a gene-informed approach. Methods: A new analysis pipeline, called “Analysis Tool for Local Association of Neuronal Transcript Expression” (ATLANTE), was generated and validated. The pipeline identifies brain regions based on the shared high expression of user-generated gene lists; in this study, the pipeline was applied to discover brain regions that may be significant to MD. Results: Nine discrete brain regions of interest to MD were identified, including the temporal pole, anterior transverse temporal gyrus (Heschl’s gyrus), olfactory tubercle, ventral tegmental area, postcentral gyrus, CA1 of the hippocampus, olfactory area, perirhinal gyrus, and posterior insular cortex. The application of network and clustering analyses identified genes of special importance, including, most notably, PRKN. Conclusions: This study provides two major insights. The first is that several brain regions have unique MD-associated genetic architectures, indicating a potential explanation for subtype-specific dysfunction. The second insight is that the PRKN gene, which is strongly associated with Parkinson’s disease, is a key player amongst the MD-associated genes. These findings reveal novel targets for the clinical screening of depression and reinforce a mechanistic connection between MD and Parkinson’s disease. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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9 pages, 616 KiB

Open AccessArticle

Two Decades of Huntington’s Disease in Varna, Bulgaria: A Retrospective Single-Centre Study of Clinical Trends and Challenges

by Mariya Levkova, Mihael Tsalta-Mladenov, Milena Stoyanova, Mari Hachmeriyan, Lyudmila Angelova and Ara Kaprelyan

Neurol. Int. 2025, 17(6), 95; https://doi.org/10.3390/neurolint17060095 - 18 Jun 2025

Viewed by 390

Abstract

Background: Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. Despite advances in understanding its molecular basis, epidemiological data in many countries, including Bulgaria, remain limited. This study aims to present [...] Read more.

Background: Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. Despite advances in understanding its molecular basis, epidemiological data in many countries, including Bulgaria, remain limited. This study aims to present clinical and genetic findings from a 20-year single-centre cohort. Methods: A retrospective review was conducted of patients evaluated for HD at the University Hospital “St. Marina” in Varna between 2004 and 2024. Data included demographics, CAG repeat length, clinical features, imaging, and psychiatric assessments. Statistical analysis focused on correlations between variables, with significance set at p < 0.05. Results: Out of 79 referred individuals, 43 were molecularly confirmed. The mean age of onset was 43 years, with a four-year diagnostic delay. The average CAG repeat length was 44.6, though two symptomatic patients had reduced penetrance alleles (38 and 39 repeats). Cognitive and psychiatric symptoms were each present in 72% of cases. Depression was significantly more prevalent in women (p = 0.011). Most patients had a positive family history, predominantly maternal. Conclusions: Our findings highlight diagnostic delays, gender-specific psychiatric vulnerabilities, and the importance of personalized care. Improved access to genetic counselling and early diagnosis are essential for optimizing outcomes. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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30 pages, 555 KiB

Open AccessReview

Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions

by Dhruba Podder, Olivia Stala, Rahim Hirani, Adam M. Karp and Mill Etienne

Neurol. Int. 2025, 17(6), 94; https://doi.org/10.3390/neurolint17060094 - 18 Jun 2025

Viewed by 924

Abstract

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in [...] Read more.

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article

(This article belongs to the Section Pain Research)

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17 pages, 1429 KiB

Open AccessArticle

Effects of Motor Preparation on Walking Ability in Active Ankle Dorsiflexion

by Hiroki Ito, Hideaki Yamaguchi, Ryosuke Yamauchi, Ken Kitai, Kazuhei Nishimoto and Takayuki Kodama

Neurol. Int. 2025, 17(6), 93; https://doi.org/10.3390/neurolint17060093 - 17 Jun 2025

Viewed by 534

Abstract

Background/Objectives: This study aimed to examine the influence of brain activity during motor preparation on walking ability, focusing on motor control during active ankle dorsiflexion. Methods: Participants were classified into high- and low-corticomuscular coherence (CMC), an index of neuromuscular control based on the [...] Read more.

Background/Objectives: This study aimed to examine the influence of brain activity during motor preparation on walking ability, focusing on motor control during active ankle dorsiflexion. Methods: Participants were classified into high- and low-corticomuscular coherence (CMC), an index of neuromuscular control based on the median value. Biomechanical and neurophysiological indices of active ankle dorsiflexion and walking ability were compared between the two groups. Additionally, a machine learning model was developed to accurately predict the CMC classification using brain neural activity during motor preparation. Results: The Cz-TA CMC (beta frequency band) during active ankle dorsiflexion successfully detected significant differences in the maximum dorsiflexion angle, inversion angular velocity, brain activity localization, and variations in Cz beta power values during the transition from motor preparation to execution. Furthermore, CMC identified significant differences in dorsiflexion angle changes after toe-off and inversion angles at initial contact during gait. A support-vector machine model predicting high or low CMC demonstrated high accuracy (Accuracy: 0.96, Precision: 0.92–1.00, Recall: 0.91–1.00, F1 Score: 0.95–0.96) during motor execution based on beta power values from −500 to 0 ms prior to the initiation of active ankle dorsiflexion (representing motor preparation). Conclusions: These findings highlight that the motor preparation processes of the brain during active ankle dorsiflexion are involved in walking ability and can be used to predict it. This indicator is independent of disease severity and holds the potential to provide a clinically versatile evaluation method. Full article

(This article belongs to the Topic Advances in Neurorehabilitation)

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20 pages, 1278 KiB

Open AccessReview

Global Diseases Deserve Global Solutions: Alzheimer’s Disease

by Emma Twiss, Carley McPherson and Donald F. Weaver

Neurol. Int. 2025, 17(6), 92; https://doi.org/10.3390/neurolint17060092 - 14 Jun 2025

Cited by 1 | Viewed by 606

Abstract

Alzheimer’s Disease (AD) is a global issue, with increasing incidence and prevalence as the world’s population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by [...] Read more.

Alzheimer’s Disease (AD) is a global issue, with increasing incidence and prevalence as the world’s population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by the absence of cure therapies. Moreover, the risk factor relationship of dementia with rising global temperatures and air pollution further necessitates the urgency of a coordinated international response. With an extensive economic and emotional burden, AD is no longer just a disease; it is a worldwide societal crisis. This review presents five calls to action to address the AD global health emergency. First, AD research must be approached as an internationally performed activity, involving standardized data sharing, collaborative innovation, and improved access to pharmaceutical studies in low- and middle-income countries (LMICs), alongside increased diversity, inclusion, and equity in research. Second, there must be a commitment to develop universally accessible, affordable, and non-invasive diagnostic tools for AD. Third, advancements in AD therapeutics should prioritize the development of affordable agents, allowing for widespread geographic distribution. Fourth, we identify focus areas for global dementia risk reduction: sleep, head injury prevention, exercise, learning, and diet (SHIELD risk reduction strategy). Fifth, improving care for individuals with AD requires eliminating stigma through educational programs for both the public and caregivers. The escalating AD crisis demands an unprecedented global coalition in research, diagnostics, therapeutics, prevention, and education to avoid a future where the disease becomes the defining crisis of our era. Full article

(This article belongs to the Collection Brain Health Initiative: Advocacy in Global Neurology)

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21 pages, 1561 KiB

Open AccessArticle

A Multimodal Multi-Stage Deep Learning Model for the Diagnosis of Alzheimer’s Disease Using EEG Measurements

by Tuan Vo, Ali K. Ibrahim and Hanqi Zhuang

Neurol. Int. 2025, 17(6), 91; https://doi.org/10.3390/neurolint17060091 - 13 Jun 2025

Viewed by 474

Abstract

Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a [...] Read more.

Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a diagnostic tool for AD faces challenges due to its susceptibility to noise and the complexity involved in the analysis. Methods: This study introduces a novel methodology employing three distinct stages for data-driven AD diagnosis: signal pre-processing, frame-level classification, and subject-level classification. At the frame level, convolutional neural networks (CNNs) are employed to extract features from spectrograms, scalograms, and Hilbert spectra. These features undergo fusion and are then fed into another CNN for feature selection and subsequent frame-level classification. After each frame for a subject is classified, a procedure is devised to determine if the subject has AD or not. Results: The proposed model demonstrates commendable performance, achieving over 80% accuracy, 82.5% sensitivity, and 81.3% specificity in distinguishing AD patients from healthy individuals at the subject level. Conclusions: This performance enables early and accurate diagnosis with significant clinical implications, offering substantial benefits over the existing methods through reduced misdiagnosis rates and improved patient outcomes, potentially revolutionizing AD screening and diagnostic practices. However, the model’s efficacy diminishes when presented with data from frontotemporal dementia (FTD) patients, emphasizing the need for further model refinement to address the intricate nuances associated with the simultaneous detection of various neurodegenerative disorders alongside AD. Full article

(This article belongs to the Topic Translational Advances in Neurodegenerative Dementias, Second Edition)

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1 pages, 157 KiB

Open AccessCorrection

Correction: Latacz et al. Safety and Efficacy of Low-Dose Eptifibatide for Tandem Occlusions in Acute Ischemic Stroke. Neurol. Int. 2024, 16, 253–262

by Paweł Latacz, Tadeusz Popiela, Paweł Brzegowy, Bartłomiej Lasocha, Krzysztof Kwiecień and Marian Simka

Neurol. Int. 2025, 17(6), 90; https://doi.org/10.3390/neurolint17060090 - 11 Jun 2025

Viewed by 213

Abstract

There was an error in the original publication [...] Full article

17 pages, 782 KiB

Open AccessSystematic Review

Combined Transcranial Direct Current Stimulation and Functional Electrical Stimulation for Upper Limbs in Individuals with Stroke: A Systematic Review

by Alfredo Lerín-Calvo, Juan José Fernández-Pérez, Raúl Ferrer-Peña and Aitor Martín-Odriozola

Neurol. Int. 2025, 17(6), 89; https://doi.org/10.3390/neurolint17060089 - 9 Jun 2025

Viewed by 967

Abstract

Background: Transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) are established interventions to enhance upper limb motor function (ULMF) in people with stroke (PwS). However, evidence supporting their combined use remains limited and inconsistent. This systematic review aims to evaluate the [...] Read more.

Background: Transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) are established interventions to enhance upper limb motor function (ULMF) in people with stroke (PwS). However, evidence supporting their combined use remains limited and inconsistent. This systematic review aims to evaluate the effectiveness of combined tDCS and FES for improving ULMF, activity, and participation in PwS. Methods: A systematic search was conducted across MEDLINE, CINAHL, SPORTDiscus, CENTRAL, SCOPUS, and Web of Science from inception to December 2024. Randomized and controlled clinical trials (RCTs) involving adults (≥18 years) with acute, subacute, or chronic stroke undergoing combined tDCS and FES interventions were included. Methodological quality was assessed with the PEDro scale, and risk of bias was evaluated using the Cochrane RoB2 tool. A qualitative synthesis was performed employing a five-level evidence grading system. Results: Five RCTs involving 148 participants (mean age range: 50.6–61.2 years; 26% female) were included. Stroke chronicity ranged from 7.6 days to 27.5 months post-onset. Four studies reported significant ULMF improvements with the combined intervention. However, activity and participation outcomes were inconsistently assessed, and results remained inconclusive. Methodological quality varied, with one study rated as excellent, two as good, one as fair, and one as poor. The risk of bias was rated high or with concerns in four out of five studies. Conclusions: Based on qualitative synthesis, moderate-level evidence supports the combined use of tDCS and FES for improving ULMF in PwS. However, high variability in protocols, small sample sizes, and the increased risk of bias in most studies limit the strength of these conclusions. Standardized protocols and larger high-quality RCTs are needed to confirm the effectiveness of this combined intervention. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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9 pages, 728 KiB

Open AccessCommunication

Fatigue and Its Association with Upper Limb Function in People with Multiple Sclerosis

by Erica Grange, Davide Marengo, Rachele Di Giovanni, Giampaolo Brichetto, Margit Mueller, Andrea Tacchino, Rita Bertoni, Francesco Zagari, Angelo Pappalardo, Luca Prosperini, Rosalba Rosato, Davide Cattaneo and Claudio Solaro

Neurol. Int. 2025, 17(6), 88; https://doi.org/10.3390/neurolint17060088 - 9 Jun 2025

Viewed by 509

Abstract

Background and Objectives: This cross-sectional study investigates the association between fatigue and upper limb (UL) function in people with Multiple Sclerosis (PwMS). Methods: Adult PwMS were recruited from five Italian MS centers. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS), while [...] Read more.

Background and Objectives: This cross-sectional study investigates the association between fatigue and upper limb (UL) function in people with Multiple Sclerosis (PwMS). Methods: Adult PwMS were recruited from five Italian MS centers. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS), while UL function was assessed through the Box and Block Test (BBT), Nine-Hole Peg Test (9HPT), and Hand-Grip Strength (HGS). Data analysis included Spearman rank correlations and Mann–Whitney U tests. Results: A total of 261 participants were involved. Significant correlations were found between fatigue severity, UL function, and patient-reported manual ability. Physical and cognitive aspects of fatigue were independently related to functional impairments. Participants with clinically relevant fatigue demonstrated lower subjective UL function, poorer BBT and HGS performance, and greater HGS asymmetry. Discussion: The study underscores the complex relationship between fatigue and functional impairments in MS. The findings suggest both strength and dexterity contribute to the perception of clinically relevant fatigue in PwMS, highlighting the importance of incorporating both domains to complement neurological assessment. Conclusion: Fatigue in PwMS is linked to both subjective and objective measures of UL function. Assessing strength and dexterity alongside fatigue may enhance clinical understanding and inform targeted rehabilitation strategies. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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10 pages, 731 KiB

Open AccessArticle

The C/C Genotype of the C-1019G (rs6295) Polymorphism of the 5-HT1A Receptor Gene Is Associated with Lower Susceptibility to Depressive Symptoms in a Rural Population in Mexico

by Margarita Hernandez-Mixteco, Olga Lidia Valenzuela, Cecilia Luz Balderas-Vazquez, Paola Castillo-Juárez, Sandra Rivera-Gutiérrez, Rocío Liliana García-Reyes, Gilberto Cornejo-Estudillo, Ricardo Jiovanni Soria-Herrera, Moises León-Juárez, Addy Cecilia Helguera-Repetto, Daniel Valencia-Trujillo, Victoria Campos-Peña, Eliud Alfredo Garcia-Montalvo and Jorge Francisco Cerna-Cortés

Neurol. Int. 2025, 17(6), 87; https://doi.org/10.3390/neurolint17060087 - 31 May 2025

Viewed by 1476

Abstract

Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% [...] Read more.

Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% of the population exhibits depressive symptoms. Previous studies have suggested that susceptibility to depression may be associated with the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene. Objective: In this study, we aimed to evaluate the association between the C-1019G polymorphism and depressive symptoms in a rural Mexican population. Methods: Using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), we examined the effect of C-1019G on depression symptoms, as evaluated by the Beck Depression Inventory. Data were obtained from 83 volunteers; individuals with depressive symptoms and those with a healthy mood were compared. Results: The results showed that the homozygous C/C genotype was found significantly more frequently in the control group than in individuals with depressive symptoms, particularly among men, and is thus associated with a decreased risk of depressive symptomatology. Conclusions: The C/C genotype could protect against susceptibility to developing depressive symptoms in a rural population in Mexico. Full article

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10 pages, 3631 KiB

Open AccessCase Report

Idiopathic Normal-Pressure Hydrocephalus Revealed by Systemic Infection: Clinical Observations of Two Cases

by Shinya Watanabe, Yasushi Shibata, Kosuke Baba, Yuhei Kuriyama and Eiichi Ishikawa

Neurol. Int. 2025, 17(6), 86; https://doi.org/10.3390/neurolint17060086 - 30 May 2025

Viewed by 761

Abstract

Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in [...] Read more.

Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients. Full article

(This article belongs to the Section Brain Tumor and Brain Injury)

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11 pages, 466 KiB

Open AccessArticle

Gender Differences in Obstructive Sleep Apnea: A Preliminary Clinical and Polysomnographic Investigation

by Alessandra Castelnuovo, Sara Marelli, Salvatore Mazzeo, Francesca Casoni, Paola Proserpio, Alessandro Oldani, Alessandro Bombaci, Elisa Bortolin, Giulia Bruschi, Federica Agosta, Massimo Filippi, Luigi Ferini-Strambi and Maria Salsone

Neurol. Int. 2025, 17(6), 85; https://doi.org/10.3390/neurolint17060085 - 29 May 2025

Viewed by 1090

Abstract

Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown. [...] Read more.

Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown. This study aimed to investigate the neuropsychological and polysomnographic (PSG) differences between OSA females and males in order to detect the impact of gender on clinical manifestation and PSG features. Methods: Data were collected from 28 OSA patients (14 females and 14 males matched for age, education, and disease severity). All patients performed a complete neuropsychological evaluation, Epworth sleepiness scale, and whole-night PSG. To evaluate the relationship between specific sleep profiles and cognitive performance, PSG parameters were correlated to scores obtained on neuropsychological tests. Results: Both male and female groups performed within the normal range across all administered neuropsychological tests, according to Italian normative values. Compared with OSA males, female patients showed significantly lower values on the Rey–Osterrieth Complex Figure (ROCF) Recall Test. By contrast, no significant statistical clinical difference emerged between the two OSA groups in terms of clinical manifestation and sleep parameters. Conclusions: This study improves the knowledge on gender-related cognitive impairment in OSA patients. Our preliminary findings demonstrate that the ROCF Recall Test may be altered in OSA females, but not in males. Further longitudinal studies are needed to investigate whether OSA female patients will develop a frank dementia over time. Full article

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18 pages, 2404 KiB

Open AccessArticle

Treatment-Associated Neuroplastic Changes in People with Stroke-Associated Ataxia—An fMRI Study

by Patricia Meier, Christian Siedentopf, Lukas Mayer-Suess, Michael Knoflach, Stefan Kiechl, Gudrun Sylvest Schönherr, Astrid E. Grams, Elke R. Gizewski, Claudia Lamina, Malik Galijasevic and Ruth Steiger

Neurol. Int. 2025, 17(6), 84; https://doi.org/10.3390/neurolint17060084 - 29 May 2025

Viewed by 1033

Abstract

Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke [...] Read more.

Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke patients with ataxic symptoms, to follow up on changes in motor function and balance due to recovery and rehabilitation, and to investigate the different effects of two treatment methods on neuronal plasticity. Methods: Therefore, fMRI-paradigms foot tapping and the motor imagery (MI) of a balancing task (tandem walking) were employed. Results: The paradigms investigated were suitable for ataxic stroke patients to monitor changes in neuroplasticity while revealing increased activity in the primary motor cortex (M1) and the cerebellum over 3 months of treatment. Furthermore, analysis of the more complex balance task revealed augmented activation of association areas due to training. Coordination exercises, constituting a specific treatment of ataxic symptoms, indicate more consolidated brain activations, corresponding to a faster motor learning process. Activation within Brodmann Area 7 has been prominent among all paradigms, indicating a special importance of this region for coordinative functions. Conclusions: Further studies are needed to confirm our results in larger patient groups. Clinical Trial Registration: German Clinical Trials Registry (drks.de). Identifier: DRKS00020825. Registered 16.07.2020. Full article

(This article belongs to the Topic Advances in Exercise-Induced Neurogenesis, Neuronal and Functional Adaptations in Neurorehabilitation)

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18 pages, 930 KiB

Open AccessReview

Ketamine in Status Epilepticus: How Soon Is Now?

by Giuseppe Magro

Neurol. Int. 2025, 17(6), 83; https://doi.org/10.3390/neurolint17060083 - 28 May 2025

Viewed by 1291

Abstract

Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a [...] Read more.

Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a framework designed by the author to recognize cases of probable benzodiazepine-resistant status epilepticus even before treatment initiation. These cases include Prolonged SE (SE lasting > 10 min), the absence of prominent motor phenomena, and acute etiology (primary central nervous system etiologies most of all). BDZ-refractory SE cases (Stage 1 Plus) might require a different approach, one targeting the unresponsive GABA signaling state mediated by NMDA/AMPA receptors, such as combined polytherapy with Ketamine from the start. These considerations stem from the receptor trafficking hypotheses: in prolonged seizure activity and primary central nervous system etiologies, GABA receptors get internalized and move away from synapses, and therefore, SE becomes resistant to BDZ. A rational polytherapy that might restore the unresponsiveness to BDZ in SE should include NMDA antagonists, such as Ketamine. Ketamine has proven effective in many experimental models of status epilepticus, and much evidence is gathering supporting its use in humans, especially in refractory and super-refractory SE. We lack studies evaluating combined polytherapy in SE, especially in the early phases. The author suggests here that Ketamine should be used along with first-line BDZ in the early SE stage falling in the category of Stage 1 Plus and as a first-line anesthetic infusion drug in refractory SE, especially in cases progressing from Stage 1 Plus, eventually adding continuous midazolam/propofol infusion in later phases. This systematic review’s objective is to summarize the presently available evidence of the early use of combined polytherapy that includes Ketamine, along with the currently available evidence of Ketamine use in early, established, and refractory SE. Nine studies were included. Boluses of Ketamine and Midazolam are effective in pediatric convulsive Stage 1 Plus SE. The results show that earlier Ketamine administration (especially within 12 h of SE onset) was significantly associated with improved seizure control, with a more favorable safety profile than Midazolam in refractory SE. Notably, a dosage of less than 0.9 mg/kg/h proves ineffective in terminating SE. Ketamine has the advantage of preventing intubation, possibly shortening the length of stay in the intensive care unit. Full article

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16 pages, 1222 KiB

Open AccessArticle

The Impact of Hypertension and Related Risk Factors on the Onset and Resolution Rates of Benign Paroxysmal Positional Vertigo Recurrence: A 6-Year Retrospective Study

by Alessandro Micarelli, Ivan Granito, Riccardo Xavier Micarelli and Marco Alessandrini

Neurol. Int. 2025, 17(6), 82; https://doi.org/10.3390/neurolint17060082 - 25 May 2025

Viewed by 1014

Abstract

Background/Objectives: Due to conflicting results about hypertension and the involvement of associated risk factors in the presentation of idiopathic benign paroxysmal positional vertigo recurrence (R-BPPV), this study aimed to explore possible associations between the resolution rate (RR) and recurrence onset (RO) of R-BPPV, [...] Read more.

Background/Objectives: Due to conflicting results about hypertension and the involvement of associated risk factors in the presentation of idiopathic benign paroxysmal positional vertigo recurrence (R-BPPV), this study aimed to explore possible associations between the resolution rate (RR) and recurrence onset (RO) of R-BPPV, as well as hypertension classification and stages and demographic characteristics. Methods: A total of 1201 medical records from patients collected over a 6-year span who first presented with R-BPPV were retrospectively evaluated regarding blood pressure (BP) presentation and associated risk factors. R-BPPV included patients treated with necessary canalith repositioning procedures (CRPs) and followed up with for 12 months. The RO and RR were evaluated when comparing patients sub-grouped by current classification and staging. The association between the RO and RR and many prognostic factors, including the presence of cardio- and neuro-vascular risks, was examined via multiple regression analysis. Results: Among the 857 included patients with R-BPPV, 211 presented with an optimal/normal BP, 210 were found to have a high–normal BP, 222 were classified with Grade 1 hypertension, and 214 were found to have Grade 2 hypertension. Significant (p < 0.05) progressive earlier presentations and increases in needed CRPs were found with the respective increase in BP subgroups. For the RO, the correlation was statistically significant for age and gender, while for the RR, the correlation was statistically significant for age and hypertension stage. Conclusions: This study demonstrates for the first time that clinical consequences of R-BPPV are strongly associated with cardio-, neuro-vascular, and socio-demographic risk factors, which are commonly involved in R-BPPV occurrence. Full article

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23 pages, 886 KiB

Open AccessReview

Reciprocal Interactions Between Periodontal Disease and Alzheimer’s Disease: Implications for Mutual Triggering, Exacerbation, and Treatment Interventions—A Comprehensive Review of the Literature

by Shatha Gharaibeh, Alameen Alsabbah, Ahmad Alloubani and Abeer Gharaibeh

Neurol. Int. 2025, 17(6), 81; https://doi.org/10.3390/neurolint17060081 - 24 May 2025

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Abstract

Periodontal health is connected to many systemic diseases, such as cardiovascular, diabetes mellitus, and neurodegenerative diseases. The oral–brain axis has gained increasing interest in the pathogenesis of diseases. Emerging studies have highlighted the potential role of periodontal disease in the development and progression [...] Read more.

Periodontal health is connected to many systemic diseases, such as cardiovascular, diabetes mellitus, and neurodegenerative diseases. The oral–brain axis has gained increasing interest in the pathogenesis of diseases. Emerging studies have highlighted the potential role of periodontal disease in the development and progression of Alzheimer’s disease. However, Alzheimer’s disease also affects periodontal disease and oral health. In this review, we address the correlation between the two diseases and the mechanisms by which one contributes to the other. Exploring the correlation between Alzheimer’s disease and periodontal disease will assist in better understanding the pathophysiology of diseases and pave the way for the development of therapeutic and preventive strategies. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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11 pages, 643 KiB

Open AccessArticle

Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy

by Joseph A. Shrader, Allison C. Niemic, Rafael Jiménez-Silva, Joshua G. Woolstenhulme, Galen O. Joe, Uma Jacobs, Ashwini Sansare, Angela Kokkinis, Kenneth Fischbeck, Chris Grunseich and Cris Zampieri

Neurol. Int. 2025, 17(6), 80; https://doi.org/10.3390/neurolint17060080 - 23 May 2025

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Abstract

Introduction: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked, progressive neuromuscular disease caused by abnormal CAG trinucleotide expansion in the androgen receptor gene. Patients with SBMA report difficulty with falls on self-reported activities of daily living scales. To our knowledge, no [...] Read more.

Introduction: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked, progressive neuromuscular disease caused by abnormal CAG trinucleotide expansion in the androgen receptor gene. Patients with SBMA report difficulty with falls on self-reported activities of daily living scales. To our knowledge, no study has examined the relationship between falls and common clinical measures of strength, balance, mobility, and disease biomarkers. We performed a cross-sectional analysis of an SBMA cohort. Objectives: The objectives of this study are as follows: (1) compare demographics, clinical measures, and biomarkers between patients who did and did not fall; (2) determine which measures best discriminate fallers from non-fallers; and (3) identify cutoff scores to detect patients with a higher fall risk. Design: Cross-sectional analysis was used. Outcome Measures: Disease biomarkers included blood serum creatinine, and clinical measures included the Timed Up and Go (TUG), the Adult Myopathy Assessment Tool (AMAT), and posturography, including the Modified Clinical Test of Sensory Interaction on Balance and the Motor Control Test. The Maximal Voluntary Isometric Contractions (MVICs) of four lower extremity muscles were captured via fixed-frame dynamometry. Results: We identified three clinical measures that help detect fall risk in people with SBMA. A post hoc receiver operating characteristic curve analysis helped identify cut scores for each test. Impairments of mobility (TUG > 8 s), muscle endurance (AMAT endurance subscale < 14), and muscle strength (ankle plantar flexion MVIC < 45% of predicted) were different between fallers and non-fallers, via independent t-tests. Conclusions: These three clinical tests can help detect fall risk that may help clinicians implement gait aid use or other fall prevention strategies before catastrophic falls occur. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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10 pages, 1113 KiB

Open AccessArticle

Evaluation of Sensory and Motor Function in Spinal and Bulbar Muscular Atrophy Using Quiet Stance and Reactive Postural Control

by Joseph A. Shrader, Ashwini Sansare, Allison C. Niemic, Rafael Jiménez-Silva, Joshua G. Woolstenhulme, Galen O. Joe, Uma Jacobs, Angela Kokkinis, Kenneth Fischbeck, Chris Grunseich and Cris Zampieri

Neurol. Int. 2025, 17(6), 79; https://doi.org/10.3390/neurolint17060079 - 22 May 2025

Cited by 1 | Viewed by 658

Abstract

Introduction: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by progressive muscle weakness, along with muscle cramps, tremors, and sensory neuropathy. Previous research has shown that patients with SBMA have difficulty with dynamic balance and sensory postural control during [...] Read more.

Introduction: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by progressive muscle weakness, along with muscle cramps, tremors, and sensory neuropathy. Previous research has shown that patients with SBMA have difficulty with dynamic balance and sensory postural control during quiet stance. There have been no reports on automatic postural reactions in SBMA. Objectives: In this study, we aimed (1) to augment previous findings of sensory postural control, (2) to investigate automatic postural reactions in SBMA, and (3) to explore the relationship between strength and balance. Design: A cross-sectional design was used for the analysis. Participants: The participants were fifty male individuals with a confirmed diagnosis of SBMA. Outcome Measures: Balance testing included the NeuroCom modified Clinical Test of Sensory Interaction on Balance (mCTSIB), which measures sway velocity during quiet stance, and the NeuroCom Motor Control Test (MCT), which measures the latency and strength of postural reactions following sudden perturbations. Strength testing included maximal voluntary isometric contractions measured via fixed-frame dynamometry. Results: Forty-seven out of fifty participants were able to complete the mCTSIB test, but only thirty-eight completed the MCT test. Patients who were unable to complete the MCT were significantly weaker in all lower extremity muscles compared to those who were able to complete testing. Compared to normative data, participants showed significantly higher sway velocity during quiet stance across all conditions of the mCTSIB, except when standing on foam with eyes open. They also exhibited significantly slower postural reactions in response to sudden shifts of the force plate on the MCT. Plantarflexor weakness was significantly correlated with poor postural control on the mCTSIB and MCT. Conclusions: This study confirms previously reported abnormalities of sensory postural control in SBMA and highlights patients’ heavy reliance on visual inputs for postural control. Additionally, this study shows that automatic postural corrections are slower than normal in SBMA and provides a unique approach for measuring the combined sensory and motor components of the disease. Both the sensory and automatic balance abnormalities were found to be associated with plantarflexor weakness and may contribute to a higher risk of falls under challenging situations. Therefore, addressing this weakness may be an important step toward fall prevention in this population. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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Neurol. Int., Volume 17, Issue 6 (June 2025) – 18 articles

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