Motor Impairment Research Articles

Age-related differences in eye movements and the association with Archimedes spiral tracing performance in young and older adults.

Age-related hand motor impairments may critically depend on visual information though few studies have examined eye movements during tasks of hand function in older adults. The purpose of this study was to assess eye movements and their association with performance while tracing on a touchscreen in young and older adults. Eye movements of 21 young (age 20-38 years; 12 females, 9 males) and 20 older (65-85 years; 10 females, 10 males) adults were recorded while performing an Archimedes spiral tracing task, a common clinical assessment sensitive to age-associated impairments in hand function. Participants traced an Archimedes spiral template on a touchscreen as accurately as possible under three conditions, using (1) a stylus, (2) the index finger, and (3) the index finger while performing a visuospatial dual task. Older adults made fewer total fixations than young adults, and participants made fewer fixations when tracing parts of the spiral where vision of the spiral template was likely more obstructed by the hand. Inter-fixation distance and inter-fixation distance variability were greater in older compared to young adults. A relationship between increased inter-fixation distance and increased spiral tracing error demonstrates the association between age-related changes in eye movements and spiral tracing performance in older adults. Results contribute novel findings of age-associated changes in ocuomotor behavior during a common clinical assessment and offer insight into motor control in older adults.

Lysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination. Therefore, in the present study, the expression level of CS-2 has been evaluated in lysophosphatidylcholine (LPC)-challenged primary astrocytes in the presence of anti-demyelinating agents such as Fingolimod, a clinically approved anti-demyelinating drug, and Ursolic Acid (UA), an experimentally accepted anti-demyelinating agent, in MS. LPC (150µg/ml) caused astrocytopathy evident by decrease in percentage of viable astrocytes, increase in percentage of apoptotic astrocytes, increase in the level of reactive oxygen species (ROS), and increase in the level of activated astrocytes. Interestingly, LPC significantly increased the expression level of CS-2 in the primary culture of astrocytes where as fingolimod and UA (1, 10, and 100µM) were able to attenuate the extent of LPC-induced astrocytopathy in the primary culture model of MS. Further, both the drugs drastically reduced the LPC-induced increase in the level of expression of CS-2 in the astrocytes. These observations indicate the fact that CS-2 could be a potential target in the management of astrocytopathy and astrocytopathy-related neurological disorders including MS. In conclusion, CS-2-targeted drugs could be potential therapeutic options in the management of MS.

Durable suppression of seizures in a preclinical model of KCNT1 genetic epilepsy with divalent small interfering RNA.

Gain-of-function variants in the KCNT1 gene, which encodes a sodium-activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression of seizures in a genetic mouse model of KCNT1 epilepsy by reducing Kcnt1 transcript with divalent small interfering RNA (siRNA), an emerging variant of oligonucleotide technology developed for the central nervous system. The ATL-201 molecule is two identical synthetic double-stranded siRNAs, covalently linked, with 100% nucleotide base pair match to sequence present in both human KCNT1 and mouse Kcnt1 that does not contain any known pathogenic variant. ATL-201 activity was tested in cortical neurons cultured from wild-type mice and in mice homozygous for Kcnt1-Y777H, the mouse ortholog to the human pathogenic KCNT1-Y796H missense variant. Seizures and nest-building behavior were measured in freely behaving Kcnt1-Y777H mice. The number and duration of seizures were measured by electrocorticography in mice dosed with ATL-201 or phosphate-buffered saline in a 6-month durability study and in a 2-month dose-efficacy study. In vitro, ATL-201 reduced KCNT1 transcript from whole-cell lysate and eliminated potassium currents from KCNT1 channels in heterologous expression. ATL-201 also eliminated sodium-activated potassium currents recorded from individual cortical neurons. Invivo, ATL-201 suppressed seizures in Kcnt1-Y777H homozygous mice in a dose-dependent manner with near-complete suppression from 2 weeks to at least 4 months. Kcnt1-Y777H mice had defects in nest building, whereas in ATL-201-treated mice nest building was equivalent to wild-type mice. Patients with KCNT1-driven epilepsy experience up to hundreds of seizures per day and have severe impairment in cognitive, motor, and language development and high mortality. The dose-dependent efficacy and long durability of ATL-201 in mice show promise for ATL-201 as a disease-modifying treatment of KCNT1 epilepsy.

Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination.

The integrity of the myelin sheath of the spinal cord (SC) is essential for motor coordination. Seipin is an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue and motor neurons in the SC. It was reported Seipin deficiency induced lipid dysregulation and neurobehavioral deficits, but the underlying mechanism, especially in SC, remains to be elucidated. In present study, we found that Seipin and myelin basic protein (MBP) increased synchronously in SC of developmental stage of mice. Demyelination impaired motor coordination as well as MBP and Seipin expression, which were alleviated by remyelination. Moreover, Seipin deficiency impaired motor coordination of mice, accompanied by hypomyelination in spinal cord. Mechanistically, we further demonstrated that myelin content as labeled by Fluormyelin, myelin basic protein (MBP) was down-regulated by Seipin deficiency. Seipin deficiency led to reduction of myelin-forming oligodendrocytes (OLs) density in spinal cord. Notably, administration of rosiglitazone (RG), a classic PPARγ activator, successfully restored the phenotypes manifested by Seipin deficiency including reduced OLs density, hypomyelination, as well as motor dyscoordination. In summary, present study revealed that Seipin deficiency disrupted motor coordination by compromising myelination in SC, and RG treatment could rescue the phenotypes. This study throws light on the mechanism underlying Seipin deficiency associated disorders and paves ways for developing therapeutics toward those diseases.

Exploring Motor–Cognitive Interference Effects and the Influence of Self-Reported Physical Activity on Dual-Task Walking in Parkinson’s Disease and Healthy Older Adults

Introduction: Parkinson’s disease (PD) is characterized by motor and cognitive impairments that often manifest as distinct motor subtypes: Postural Instability Gait Difficulty (PIGD) and Tremor-Dominant (TD). Motor–cognitive interference, especially under dual-task (DT) walking conditions, may vary by subtype, providing insights into specific impairments. This study explored DT interference effects in PD subtypes, focusing on the potential impact of self-reported physical activity, which may help mitigate subtype-specific impairments and improve motor–cognitive function. Methods: PD patients classified as PIGD or TD and healthy controls completed single-task (ST) and DT walking assessments involving different cognitive tasks (Serial Subtraction, Auditory Stroop, and Clock Task). Physical activity levels were evaluated using the CHAMPS questionnaire, analyzing the self-reported frequency and duration of weekly exercise-related activities. Results: Interference effects were significantly different between PD patients and controls, with the PIGD group showing greater motor impairment under high cognitive load, primarily affecting gait, than the TD and control groups. Performance differences between groups diminished as cognitive load increased. Self-reported physical activity does not significantly moderate motor performance under DT conditions, suggesting that activity levels in this sample are insufficient to offset motor–cognitive interference. However, like group affiliation, physical activity directly influences motor performance during DT conditions, indicating that both factors independently impact motor–cognitive function in PD. Discussion: These findings suggest that DT assessments help differentiate PD motor subtypes, as group differences were minimal in ST conditions. While physical activity is associated with general improvements in motor ST and DT performance in PD and controls, the lack of a significant moderating effect from self-reported exercise-related physical activity indicates that current activity levels may not be high enough to counter motor–cognitive interference. More intensive or DT-specific exercise may be required to reduce interference effects. Future research should examine the role of structured physical activity programs, potentially incorporating DT training, to evaluate their impact on motor–cognitive interference in PD.

Icaritin alleviates motor impairment and osteoporosis in Parkinson’s disease mice via the ER-PI3K/Akt pathway

This study investigates the role of flavonoid Icaritin (ICT) in estrogen-deficient ovariectomized (OVX) female mice by activating the Estrogen receptor (ER)/ Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, potentially delaying Parkinson’s disease (PD) progression post-castration. Seventy-five 8-week-old C57BL/6J female mice underwent ovariectomy, followed by MPTP (20 mg/kg) injection for 7 days. ICT (20 mg/kg) was administered for 14 days, and motor function was assessed using various behavioral tests. Serum estradiol, FSH, LH levels were measured by ELISA, and the expression of PI3K/Akt signaling and apoptosis proteins was analyzed by Western blot. Bone mineral density was assessed via dual-energy X-ray absorption, and histology of the uterus and femur was performed. Results showed that ICT alleviated MPTP-induced motor deficits, increased serum estradiol, and improved uterine atrophy. At the molecular level, ICT activated the PI3K/Akt pathway, reduced apoptosis, and mitigated PD symptoms and osteoporosis induced by OVX. These findings suggest ICT may offer therapeutic potential in managing OVX-induced motor dysfunction and PD.

EEG Responses to Upper Limb Pinprick Stimulation in Acute and Early Subacute Motor and Sensorimotor Stroke: A Proof of Concept.

Electroencephalogram (EEG) during pinprick stimulation has the potential to unveil neural mechanisms underlying sensorimotor impairments post-stroke. A proof-of-concept study explored event-related peak pinprick amplitude and oscillatory responses in healthy controls and in people with acute and subuacutemotor and sensorimotor stroke, their relationship, and to what extent EEG somatosensory responses can predict sensorimotor impairment. In this study, 26 individuals participated, 10 people with an acute and early subacute sensorimotor stroke, 6 people with an acute and early subacute motor stroke, and 10 age-matched controls. Pinpricks were applied to the dorsa of the impaired hand to collect somatosensory evoked potentials. Time(-frequency) analyses of somatosensory evoked potential (SEP) data at electrodes C3 and C4 explored peak pinprick amplitude and oscillatory responses across the three groups. Also, in stroke, (sensori-)motor impairments were assessed with the Fugl Meyer Assessment Upper Extremity (FMA) and Erasmus modified Nottingham Sensory Assessment (EmNSA) at baseline and 7 to 14days later. Mixed model analyses were used to address objectives. It was demonstrated that increased beta desynchronization magnitude correlated with milder motor impairments (R2adjusted = 0.213), whereas increased beta resynchronization and delta power were associated to milder somatosensory impairment (R2adjusted = 0.550). At the second session, larger peak-to-peak SEP amplitude and beta band resynchronization at baseline were related to greater improvements in EMNSA and FMA scores, respectively, in the sensorimotor stroke group. These findings highlight the potential of EEG combined with somatosensory stimuli to differentiate between sensorimotor and motor impairments in stroke, offering preliminary insights into both diagnostic and prognostic aspects of upper limb recovery.

Motor and visuospatial processing profile in a cross-conditions study: A comparison between developmental coordination disorder and nonverbal learning disability.

Neurodevelopmental conditions often exhibit overlapping symptoms, posing challenges for differential diagnosis. Developmental Coordination Disorder (DCD) manifests as fundamental motor impairments, often along with co-occurring visuospatial difficulties. Nonverbal Learning Disorder (NLD) features visuospatial core challenges, with a less consistent characterization of its motor profile. Strikingly, to date no study has directly compared DCD and NLD profiles. The present study aimed to analyze whether DCD and NLD share any characteristics by contrasting their motor and visuospatial performances, comparing them with non-diagnosed (ND) peers. A total of 102 participants (8-16 years; DCD N = 29, NLD N = 29, ND N = 44) completed motor and visuospatial tasks. The groups' performance was compared, and the discriminatory power of the measures administered was analyzed. Our findings support the substantial motor and visuospatial impairments in DCD and NLD, respectively. Regarding diagnostic efficacy, motor and visuospatial tasks effectively differentiated DCD or NLD from ND, with specificities related to each condition. Balance, and to a lesser extent, Spatial Processing revealed significant predictive power in distinguishing between DCD and NLD. Our results revealed cross-disorder similarities and highlighted specific hallmarks, corroborating the need of a comprehensive motor and visuospatial assessment for distinguishing between DCD and NLD.

Depth-sensor-based shared control assistance for mobility and object manipulation: toward long-term home-use of BCI-controlled assistive robotic devices.



Objective. Assistive robots can be developed to restore or provide more autonomy for individuals with motor impairments. In particular, power wheelchairs can compensate lower-limb impairments, while robotic manipulators can compensate upper-limbs impairments. 
Recent studies have shown that Brain-Computer Interfaces (BCI) can be used to operate this type of devices.
However, activities of daily living and long-term use in real-life contexts such as home require robustness and adaptability to complex, changing and cluttered environments which can be problematic given the neural signals that do not always allow a safe and efficient use. Approach. This article describes assist-as-needed sensor-based shared control methods relying on the blending of BCI and depth-sensor-based control.
The proposed assistance targets the BCI-teleoperation of effectors for tasks that answer mobility and manipulation needs in a at-home context. Main Results. The assistance provided by the proposed methods was evaluated through a wheelchair mobility and reach-and-grasp laboratory-based experiments in a controlled environment, as part of a clinical trial with a quadriplegic patient implanted with a wireless 64-channel ElectroCorticoGram (ECoG) recording implant named WIMAGINE.
Results showed that the proposed methods can assist BCI users in both tasks.
Indeed, the time to perform the tasks and the number of changes of mental tasks were reduced. Moreover, unwanted actions, such as wheelchair collisions with the environment, and gripper opening that could result in the fall of the object were avoided. 
Significance. The proposed methods are steps toward at-home use of BCI-teleoperated assistive robots. Indeed, the proposed shared control methods improved the performance of the two assistive devices. Clinical trial, registration number: NCT02550522.

Impact of Brain Lesion Characteristics on Motor Function and Cortical Reorganization in Hemiplegic Cerebral Palsy

Background and Objectives: Hemiplegic or unilateral cerebral palsy (UCP) is primarily characterized by motor impairment, mainly affecting the upper limb. Research has centered on factors influencing the varying degrees of motor deficit in UCP, using neuroscience advancements for in vivo exploration of brain structure (morphometry) and cortical reorganization (functional magnetic resonance imaging (fMRI)). This study aims to evaluate functional activation in the motor cortex in UCP and to explore how lesion characteristics and timing affect neuroplasticity and motor function. Materials and Methods: Between 2017 and 2021, structural and functional MRIs were performed on 44 UCP patients (mean age 15.5 years, 24 males, 20 females), all with Manual Ability Classification System (MACS) levels I-III and Intelligence Quotient (IQ) ≥ 50. The lesion characteristics of size, type, and time of occurrence (ante-, peri-, or early postnatal) were analyzed. An association was sought between the characteristics of the lesion and the degree of motor deficit of the upper limb, as determined by the MACS level. fMRI assessed cortical activation during a finger-tapping task for the paretic hand and compared activation patterns based on lesion characteristics. Results: Six lesion types were identified, with arterial ischemic stroke being the most common and largest in volume. Lesion size strongly correlated with patients’ MACS levels, while lesion type and timing showed no association with the severity of motor impairment classified by MACS. Motor reorganization varied, with activation occurring ipsi-, contra-, or bilaterally to the affected hand, depending on lesion size and type. Smaller, subcortical lesions primarily showed ipsilesional activation, while larger, cortical lesions did not exhibit a specific group activation, possibly due to varying individual reorganization. No association was found between the lesion timing and the reorganization model. Conclusions: Motor functional reorganization in UCP is closely linked to lesion characteristics, with smaller, subcortical lesions favoring typical organization in the contralateral motor cortex. The timing of the lesion does not significantly affect cortical reorganization. Lesion size was a key determinant of motor function, whereas lesion type (e.g., ischemic stroke) and timing (early vs. late occurrence) were less critical for predicting functional outcome.

Effects of mirror therapy on motor and functional recovery of the upper extremity in subacute stroke: Systematic review and meta-analysis.

To review and synthesize existing evidence on the effect of mirror therapy (MT) on motor and functional recovery and the effect of unimanual and bimanual MT in individuals with subacute stroke. PubMed, Physiotherapy Evidence Database, Cochrane, and Airiti Library were searched for relevant studies. Randomized and pilot randomized controlled trials comparing MT with sham MT or conventional therapy were included. Three researchers independently reviewed eligible studies for study design, participants' characteristics, intervention, and outcome measures and assessed study quality. The Physiotherapy Evidence Database scale was used to evaluate the methodological quality of included studies, and the Cochrane Risk of Bias Tool was used to assess the risk of bias. Fifteen studies with 546 participants were included. An overall effect of MT was found for motor impairment (effect size [95% confidence interval]: 0.473 [0.274-0.673], p < .001), motor function (0.266 [0.059-0.474], p = .012), and activities of daily living (ADL) (0.461 [0.25-0.671], p < .001), compared with controls. There was a significant difference in motor impairment (0.39 [0.134-0.647], p = .003), motor function (0.298 [0.003-0.593], p = .048), and ADL (0.461 [0.157-0.766], p = .003) in favor of bimanual MT compared with controls. No significant effect was found for unimanual MT. MT, specifically bimanual MT, is an effective intervention for improving motor recovery, motor function, and ADL in individuals with subacute stroke, whereas unimanual MT does not show significant benefits in these areas.

The Intrauterine Treatment of Open Spinal Dysraphism.

Open spinal dysraphism is a congenital malformation that causes major morbidity. Its consequences include sensory and motor impairment as well as bladder- and bowel dysfunction. It is often also associated with prenatal ventriculomegaly, which, in turn, necessitates postnatal treatment with a ventriculoperitoneal shunt in approximately 80% of cases. Prenatal therapy with coverage of neural tube defect can reduce the shunt rate and preserve motor function. In this review, we describe the different surgical procedures and their outcomes. This review is based on publications that were retrieved by a selective literature search in the MEDLINE, Web of Science, EMBASE, Scopus, and Cochrane databases, employing pertinent keywords. Studies of all types (except case reports) that were published in English or German in the period 2010-2024 were included. The randomized, controlled MOMS trial showed that intrauterine surgery for defect closure resulted in less progressive neural tissue damage than postnatal surgery and reduced the need for shunting by approximately half (40% vs. 82%). Since the publication of these results, various prenatal surgical procedures have been established, including hysterotomy-assisted, percutaneous fetoscopic, and laparotomy-assisted fetoscopic closure. The individual surgical methods yield comparable results in terms of motor function and shunt rate. A problem with these procedures is that they increase the likelihood of preterm birth, to an extent that varies from one type of procedure to another. Prenatal surgery improves motor function and reduces the shunt rate but long-term outcomes beyond adolescence are still lacking. Transparent and interdisciplinary counseling is essential in prenatal communication to inform parents not only about the potential benefits of this treatment, but also about its limitations and risks.

Reinforcement Learning is Impaired in the Sub-acute Post-stroke Period.

In humans, most spontaneous recovery from motor impairment after stroke occurs in the first 3 months. Studies in animal models show higher responsiveness to training over a similar time-period. Both phenomena are often attributed to a milieu of heightened plasticity, which may share some mechanistic overlap with plasticity associated with normal motor learning. Given that neurorehabilitation approaches are frequently predicated on motor learning principles, here we asked if the sensitivity of trial-to-trial learning for 2 kinds of motor learning processes often involved during rehabilitation is also enhanced early post-stroke. In a cross-sectional design, we compared (1) reinforcement and (2) error-based learning in 2 groups: 1 tested within 3 months after stroke (early group, N = 35) another tested more than 6 months after stroke (late group, N = 30). These 2 forms of motor learning were assessed with variations of the same visuomotor rotation task. Critically, motor execution was matched between the 2 groups. Reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unimpaired in either group. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location. The presence of a deficit in reinforcement motor learning in the first 3 months after stroke has important implications for rehabilitation. It might be necessary to either increase reinforcement feedback given early after stroke, increase the dose of rehabilitation to compensate, or delay onset of rehabilitation approaches that may rely on reinforcement, for example, constraint-induced movement therapy, and instead emphasize other forms of motor training in the subacute time period.

Impact of diabetes mellitus type two on incidence and progression of Parkinson's disease: a systematic review of longitudinal patient cohorts.

Parkinson's disease (PD) is a chronic neurodegenerative disease of the elderly. Patients suffer from progressive motor and non-motor symptoms. Further, PD patients often present geriatric features like multimorbidity and polypharmacotherapy. A frequent comorbidity of PD patients is diabetes mellitus type two (T2DM). In the last decade growing evidence emerged on the impact of T2DM on PD. Of the present review was to analyze the impact of T2DM on PD incidence and progression in patient cohorts. A systematic review of the literature was performed via PubMed and Google Scholar. Studies on longitudinal PD patient cohorts with at least 10 patients per group were included. The diabetic state of the patient had to be determined. In total, 15 studies were analyzed for this review. According to most of the included studies T2DM increases the risk of developing PD significantly. Disease progression is augmented by T2DM both for motor and cognitive impairments. Some studies also point out a correlation of motor worsening and diabetic status measured by the serum HbA1c level. In relation to biomarkers, PD patients with diabetes have higher neurofilament light chain and Tau level but lower Amyloid beta level. T2DM seems to be a risk factor for the development and progression of PD. PD patients should be screened for T2DM and treatment should be initiated promptly. There is still a lack of knowledge about the molecular mechanisms leading to interactions of these diseases.

Clinical validation of an individualized auto-adaptative serious game for combined cognitive and upper limb motor robotic rehabilitation after stroke

BackgroundIntensive rehabilitation through challenging and individualized tasks are recommended to enhance upper limb recovery after stroke. Robot-assisted therapy (RAT) and serious games could be used to enhance functional recovery by providing simultaneous motor and cognitive rehabilitation.ObjectiveThe aim of this study is to clinically validate the dynamic difficulty adjustment (DDA) mechanism of ROBiGAME, a robot serious game designed for simultaneous rehabilitation of motor impairments and hemispatial neglect.MethodsA proof of concept, with 24 participants in subacute and chronic stroke, was conducted using a 5-day protocol (two days were dedicated to assessment and three days to consecutive training sessions). Participants performed three consecutive ROBiGAME sessions during which overall task difficulty was determined through simultaneous DDA of motor and attentional parameters. Relationships between clinical and robotic assessment scores with respective task-difficulty parameters were analyzed using a multivariate regression model and a principal component analysis.ResultsGame difficulty rapidly (within approximately thirty minutes) auto-adapted to match individual impairment levels. The relationship between task-difficulty parameters with motor (Fugl Meyer Assessment: r = 0.84 p < 0.05) and with attentional impairments (Bells test total omissions: r = 0.617 p < 0.05) showed that task-difficulty during RAT adapted to each participant’s degree of impairment. Principal component analysis identified two data subsets determining overall task-difficulty, one subset for motor and the other for cognitive functional evaluation scores with respective task-difficulty parameters.ConclusionsThis proof of concept clinically validated a DDA mechanism and showed how task-difficulty adequately adapted to match individual degrees of impairment during RAT after stroke. ROBiGAME provided simultaneous motor and attentional exercises with parameters determining task-difficulty strongly related with respective clinical and robotic evaluation scores. Individualized levels of game difficulty and rapid adjustment of the system suggest implementation in clinical practice.Registry number This study was registered at ClinicalTrials.gov (NCT02543424).

Can attention-deficit/hyperactivity disorder be considered a form of cerebellar dysfunction?

Attention-deficit/hyperactivity disorder (ADHD) is a heterogenous disorder, commonly described for presenting difficulties in sustained attention, response inhibition, and organizing goal-oriented behaviors. However, along with its traditionally described executive dysfunction, more than half of the children diagnosed with ADHD have been reported to show difficulties with gross and fine motor skills, albeit motor impairments in ADHD continue to be a neglected area of clinical attention. The rapidly growing field of the clinical cognitive neuroscience of the cerebellum has begun to relate cerebro-cerebellar circuits to neurodevelopmental disorders. While the cerebellum’s role in motor function, such as balance, motor coordination, and execution, is well recognized, ongoing research has evidenced its additional and fundamental role in neurocognitive development and executive function, including attention and social cognition, which are all areas of impairment commonly found in ADHD. Interestingly, neuroimaging studies have consistently shown differences in cerebellar volume and functional connectivity between ADHD and typically developing children. Furthermore, methylphenidate is known to act at the cerebellar level, as intrinsic cerebellar dopaminergic systems involved in attention and motor function have been identified. This article reviews some of the main findings linking cerebellar dysfunction to ADHD behavioral symptoms and incorporates the cerebellum as a possible neurological basis and differentiating indicator within the condition. We suggest considering more rigorous assessments in future ADHD studies, including cerebellar-associated skill evaluations to correlate with symptom severity and other detected outcomes, such as executive dysfunction, and study possible associative patterns that may serve as more objective measures for this diagnosis.

Mitigation of Neuroinflammation and Oxidative Stress in Rotenone-Induced Parkinson Mouse Model through Liposomal Coenzyme-Q10 Intervention: A Comprehensive In-vivo Study.

Parkinson's disease (PD) stands as the sec most prevalent incapacitating neurodegenerative disorder characterized by deterioration of dopamine-producing neurons in the substantia nigra. Coenzyme Q10 (CoQ10) has garnered attention as a potential antioxidant, anti-inflammatory agent and enhancer of mitochondrial complex-I activity. This study aimed to examine and compare the effectiveness of liposomal and non-encapsulated CoQ10 in rotenone induced-PD mouse model over a 21-day treatment duration. 30 mice were divided into 5 equal groups: Group I (mice receiving normal saline), Group II (rotenone was administered to mice), Group III (standard CoQ10 was given to mice), Group IV (mice were treated with non-encapsulated CoQ10) and Group V (mice were treated with CoQ10 Liposomes). Motor performance, the preservation of dopaminergic neurons, levels of neuroinflammation, oxidative stress, neurotransmitter levels, RT-qPCR analysis of PD-linked genes and histopathology were evaluated. The Liposomal CoQ10 group exhibited superior outcomes in behavioral tests such as reduced anxiety in the open field test, enhanced balance and coordination in beam balance test and improved cognitive performance in Y-maze test. Liposomal Coenzyme Q10 displayed pronounced antioxidative effects, evidenced by a significant (p < 0.001) increase in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities. In contrast, the non-encapsulated CoQ10 group showed a delayed response in mitigating the inflammation and oxidative stress. CoQ10 Liposomes demonstrated superior efficacy (p < 0.0001) in restoring dopamine and noradrenaline levels, reducing acetylcholinesterase activity, and downregulating Synuclein Alpha (SNCA) gene expression (0.722-fold change) compared to oral CoQ10, highlighting its potential in suppressing PD symptoms. The results of this study indicated that the liposomal CoQ10 effectively averted motor impairments, memory lapses, oxidative stress, as well as neuroinflammation triggered by rotenone.

Exploring the Pathophysiology, Diagnosis, and Treatment Options of Multiple Sclerosis.

The complicated neurological syndrome known as multiple sclerosis (MS) is typified by demyelination, inflammation, and neurodegeneration in the central nervous system (CNS). Managing this crippling illness requires an understanding of the complex interactions between neurophysiological systems, diagnostic techniques, and therapeutic methods. A complex series of processes, including immunological dysregulation, inflammation, and neurodegeneration, are involved in the pathogenesis of MS. Gene predisposition, autoreactive T cells, B cells, and cytokines are essential participants in the development of the disease. Demyelination interferes with the ability of the CNS to transmit signals, which can cause a variety of neurological symptoms, including impaired motor function, sensory deficiencies, and cognitive decline. Developing tailored therapeutics requires understanding the underlying processes guiding the course of the disease. Neuroimaging, laboratory testing, and clinical examination are all necessary for an accurate MS diagnosis. Evoked potentials and cerebrospinal fluid studies assist in verifying the diagnosis, but magnetic resonance imaging (MRI) is essential for identifying distinctive lesions in the CNS. Novel biomarkers have the potential to increase diagnostic precision and forecast prognosis. The goals of MS treatment options are to control symptoms, lower disease activity, and enhance quality of life. To stop relapses and reduce the course of the disease, disease-modifying treatments (DMTs) target several components of the immune response. DMTs that are now on the market include interferons, glatiramer acetate, monoclonal antibodies, and oral immunomodulators; each has a unique mode of action and safety profile. Symptomatic treatments improve patients' general well-being by addressing specific symptoms, including pain, sphincter disorders, fatigue, and spasticity. Novel treatment targets, neuroprotective tactics, and personalized medicine techniques will be the main focus of MS research in the future. Improving long-term outcomes for MS patients and optimizing disease treatment may be possible by utilizing immunology, genetics, and neuroimaging developments. This study concludes by highlighting the complexity of multiple MS, including its changing therapeutic landscape, diagnostic problems, and neurophysiological foundations. A thorough grasp of these elements is essential to improving our capacity to identify, manage, and eventually overcome this intricate neurological condition.

Risk factors of avascular femoral head necrosis after a pediatric femoral neck fracture: a 15-year follow up and an adjustment to the Delbet classification.

Pediatric femoral neck fractures (PFNF) are rare but associated with a high rate of serious complications such as avascular femoral head necrosis (AVN). Major risk factors and prognostic tools for an AVN are still unclear. As AVN is a devastating complication, this study aims to evaluate the predictors for AVN following a PFNF. All patients that suffered a PFNF or an AVN following a PFNF in the last 15 years that were treated at a university-level hospital with a minimum of 12 months follow-up were included in this retrospective study. Patients with a pathological fracture or closed epiphysis were excluded. Radiological outcome was evaluated based on Ratcliff criteria. The association of possible risk factors such as age, gender, traumatic mechanism, fracture type, degree of dislocation, time to surgery or type of surgical intervention with AVN was analyzed. Since not all fractures could be assigned to an exact fracture type, a new fracture type was included in the subgroup analyses. We included 37 patients in the study population. The mean age at the time of the diagnosis was 11.5 years (ranging 5-16 years). Mean follow-up was 30 months. 75% of the cases were diagnosed on the day of the trauma. Nine patients had a delayed diagnosis of which eight had a previous neurological disease (eg. cerebral palsy). A previous illness was significantly associated with a late diagnosis (p < 0.001). 17 patients suffered a high velocity trauma. 35 patients were treated operatively, the majority with a closed reduction (81%) and an internal fixation with cannulated screws (75%). In 24 patients (65%) an additional puncture of the hip joint was performed. Ten patients developed AVN, two of them ultimately had to be treated with a total hip arthroplasty. Female gender was associated with AVN, though not significantly (p = 0.051). A Delbet type IV injury and a high velocity trauma were significantly associated with an AVN (p = 0.020, p = 0.030 respectively). A type IIR fracture was significantly more likely to develop AVN compared to a Delbet type II fracture. Age, polytrauma, degree of dislocation, time to diagnosis, time to surgery and type of treatment was found were not significantly associated with AVN. Neurologically impaired patients are prone to a late diagnosis of a femoral neck fracture, mainly due to both cognitive and motor impairments. High velocity trauma is a significant risk factor for developing AVN. In contrast to literature, a Delbet type IV fracture was significantly associated with AVN. A type IIR fracture has a higher possibility to develop AVN than a normal Delbet type II fracture. As the incidence of pediatric femoral neck fractures is low, the size of a study population is limited. Nevertheless, AVN is still a life altering complication leading to additional surgical treatments, hospital stays and impairment of daily life activities. Therefore, further research is needed to better understand the mechanisms of underlying risk factors and to develop strategies for the prevention and management of AVN in the pediatric population. Hence multicenter studies with a bigger study population are crucial.

Repeated administration of a subanesthetic dose of ketamine results in impaired motor and cognitive behavior and differential expression of hippocampal P2X1 and P2X7 receptors in adult mice.

Ketamine hydrochloride serves multiple purposes, including its use as a general anesthetic, treatment for depression, and recreational drug. In studies involving rodents, ketamine is utilized as a model for schizophrenia. However, it is unclear whether age affects the behavioral response induced by repeated ketamine administration and if it modifies the expression levels of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and purinergic receptors (P2X1, P2X4, P2X7). In the present study, we evaluated the effect of intraperitoneal administration of subanesthetic ketamine dose (30mg/Kg) for fourteen days on young (35 days of age) and adult (76 days of age) mice on different behavioral tests. Nest-building behavior was evaluated during the fourteen-day treatment; short-term memory and social interaction tests were assessed twenty-four hours after the last administration of ketamine. Interestingly, only adult mice treated with ketamine showed impaired nest-building and novel object recognition tests. In the hippocampus, an area related to memory and cognition, ketamine administration showed no changes in the relative expression of GluN1, P2X4, and P2X7 while increasing GluA2 and P2X1 only in young mice. In contrast, when assessing the protein levels of P2X1 and P2X7 in the hippocampus following ketamine treatment, young mice exhibited a decrease in P2X1 levels while P2X7 levels increased. In contrast, adult mice showed the opposite pattern; P2X1 levels were higher, and P2X7 levels decreased. These results suggest that adult mice are more vulnerable to repeated ketamine administration than young mice and that a differential response of P2X1 and P2X7 might contribute to ketamine-induced behavioral changes.