Rapid Head Research Articles

Transient Increases in Alpha Power Relative to Healthy Reference Ranges in Awake Piglets After Repeated Rapid Head Rotations

Background/Objectives: Sports-related concussions are a main cause of cognitive dysfunction and somatic complaints, particularly in youth. While the majority of concussion symptoms resolve within one week, cognitive effects may persist. In this study, we sought to study changes to cognition within this acute time frame. Methods: In this current study, we use an established swine model of traumatic brain injury (TBI) to study the effects of single and repeated head rotations on resting-state electroencephalography (rs-EEG) in awake piglets in the acute (within 7 days) time period after injury. We studied both healthy and experimental groups to (1) establish healthy reference ranges (RRs; N = 23) for one-minute rs-EEG in awake piglets, (2) compare the effects of single (N = 12) and repeated head rotations (N = 13) on rs-EEG, and (3) examine the acute time course (pre-injury and days 1, 4, and 7 post-injury) in animals administered single and repeated head rotations. EEG data were Fourier transformed, and total (1–30 Hz) and relative power in the alpha (8–12 Hz), beta (16.5–25 Hz), delta (1–4 Hz), and theta (4–7.5 Hz) bands were analyzed. Results: Total power and relative alpha, beta, delta, and theta power were consistent measures across days in healthy animals. We found a significant and transient increase in relative alpha power after repeated injury on day 1 in all regions and a rise above the healthy RR in the frontal and left temporal regions. Conclusions: Future studies will expand the study duration to investigate and inform clinical prognoses from acute measurements of rs-EEG.

Impact of proprioceptive cervical dizziness in chronic neck pain syndromes on gait and stance during active head-turn challenges.

An earlier observational study described selected patients with acute neck pain syndrome, who experienced short bursts of cervical vertigo elicited by rapid head movements. The current study on a larger cohort of 20 patients with chronic or frequently recurring neck pain syndrome and age-matched controls focused on two major questions: (1) Can head movements in subjects with exacerbations of neck pain and restrictions of neck mobility also elicit bursts of vertigo? (2) What is the impact on postural balance measured by analysis of body sway and locomotion? A detailed questionnaire was applied, posture and gait were evaluated by use of instrumented posturography-and gait analysis with and without slow or rapid horizontal head rotations in the yaw plane with and without sight/visual input. All patients reported some or frequent episodes of dizziness in the range of seconds only elicited by rapid, not by slow head movements. Postural sway in patients was unremarkable in undisturbed conditions without head movements, but specifically increased by rapid but not slow head turns. The latter is best explained by the lack of continuous control of velocity and amplitude of saccadic head movements. Gait analysis revealed a slowed and cautious gait pattern already at undisturbed condition that was even exaggerated during rapid head turns. These observations demonstrate that chronic or recurrent neck pain is associated with episodic experiences of dizziness and above results in both chronic and episodic alterations of stance and gait that resemble those described for patients with phobic postural vertigo/persistent postural perceptual dizziness, a functional gait disorder.

Further insights into anti-IgLON5 disease: a case with complex clinical presentation

BackgroundAnti-IgLON5 disease is an autoimmune encephalitis overlapping with neurodegenerative disorders due to pathological accumulation of hyperphosphorylated tau. It is characterized by several clinical manifestations determined by involvement of different brain areas, and mild response to first-line immunotherapies. We report a case of anti-IgLON5 disease with a multifaceted semiology and an unusually good response to glucocorticoid monotherapy.Case presentationA 68-year-old man with type 2 diabetes was evaluated for an 8-month history of progressive gait disorder causing frequent falls. He also suffered from obstructive sleep apneas and complained of dysphonia, dysarthria, occasional dysphagia, urinary incontinence, and upper limb action tremor. Neurological examination demonstrated bilateral eyelid ptosis, limitation of ocular horizontal smooth pursuit movements, slow horizontal saccades, and lack of inhibition of the vestibulo-ocular reflex during rapid horizontal head torsions. The patient also displayed involuntary, slow, rhythmic movements of the left periorbital and perioral muscles, spreading to the ipsilateral hemipalate and hemitongue, along with bilateral negative upper limb myoclonus. There were proximal muscle wasting in the upper limbs, proximal weakness of the four limbs, and diffuse fasciculations. Ataxia of stance and gait and of the four limbs was noted. MRI of the brain and spine was unremarkable; nerve conduction studies revealed a chronic, predominantly demyelinating, sensory-motor polyneuropathy, probably due to diabetes. Routine CSF examination was unrevealing and serum GFAP level was 89.6 pg/mL; however, the autoimmunity tests revealed a high-titer positivity for anti-IgLON5 autoantibodies in both CSF and serum, leading to the diagnosis of anti-IgLON5 disease. Symptoms improved significantly after intravenous methylprednisolone.ConclusionsHemifacial and hemiorolingual myorhythmia along with peculiar oculomotor abnormalities characterizes the multifaceted clinical picture of our case. The complex semiology of our patient may reflect multifocal targeting of the autoimmune process or sequential spreading of tau inclusions in different brain areas. Our patient’s optimal response to glucocorticoid monotherapy could be underpinned by a slightly different phenotype in which autoimmunity plays a greater pathogenic role than tauopathy, with a lower burden of tau deposition. In such patients, neurodegeneration and tau accumulation could be merely secondary to immune-mediated neuronal dysfunction, supporting the existence of a group of glucocorticoid-responsive patients.

A Rapid Head Organ Localization System Based on Clinically Realistic Images: A 3D Two Step Progressive Registration Method with CVH Anatomical Knowledge Mapping.

Rapid localization of ROI (Region of Interest) for tomographic medical images (TMIs) is an important foundation for efficient image reading, computer-aided education, and well-informed rights of patients. However, due to the multimodality of clinical TMIs, the complexity of anatomy, and the deformation of organs caused by diseases, it is difficult to have a universal and low-cost method for ROI organ localization. This article focuses on actual concerns of TMIs from medical students, engineers, interdisciplinary researchers, and patients, exploring a universal registration method between the clinical CT/MRI dataset and CVH (Chinese Visible Human) to locate the organ ROI in a low-cost and lightweight way. The proposed method is called Two-step Progressive Registration (TSPR), where the first registration adopts "eye-nose triangle" features to determine the spatial orientation, and the second registration adopts the circular contour to determine the spatial scale, ultimately achieving CVH anatomical knowledge automated mapping. Through experimentation with representative clinical TMIs, the registration results are capable of labeling the ROI in the images well and can adapt to the deformation problem of ROI, as well as local extremum problems that are prone to occur in inter-subject registration. Unlike the ideal requirements for TMIs' data quality in laboratory research, TSPR has good adaptability to incomplete and non-thin-layer quality in real clinical data in a low-cost and lightweight way. This helps medical students, engineers, and interdisciplinary researchers independently browse images, receive computer-aided education, and provide patients with better access to well-informed services, highlighting the potential of digital public health and medical education.

Blood pressure variability at rest and during pressor challenges in patients with acute ischemic stroke.

Patients with acute ischemic stroke (AIS) have elevated blood pressure (BP) variability (BPV) and reduced baroreflex sensitivity (BRS) at rest for several days after initial stroke symptoms. We aimed to assess BPV and BRS in AIS patients during pressor challenge maneuvers in the acute and subacute phases of stroke. Pressor challenge maneuvers simulate day-to-day activities and can predict the quality of life. Continuous beat-to-beat BP and ECG in 15 AIS patients (mean age 69 ± 7.5 years) and 15 healthy controls (57 ± 16 years) were recorded at rest and during a 5-min rapid head positioning (RHP) paradigm. Patients were assessed within 24 h (acute phase) and 7 days (subacute phase) of stroke onset. Low frequency (LF) SBP power (measure of BPV), LF-α, and combined α-index (measure of BRS) were calculated from the recordings. In the acute phase, at rest, LF-SBP power was higher ( P = 0.024) and α-index was lower ( P = 0.006) in AIS patients than in healthy controls. There was no change in LF-SBP during RHP in the patients but in healthy controls, it increased significantly ( P = 0.018). In the subacute phase, at rest, the alpha-index increased ( P = 0.037) and LF-SBP decreased ( P = 0.029) significantly in the AIS patients, however, there was still no rise in the LF-SBP power during RHP ( P = 0.240). AIS patients have a high resting BPV. High resting BPV may be responsible for blunted BPV responses during pressor challenge maneuvers such as RHP, suggesting ongoing autonomic dysfunction and compromised quality of life.

Distinct Serum Glial Fibrillary Acidic Protein and Neurofilament Light Time-Courses After Rapid Head Rotations.

Traumatic brain injury (TBI) causes significant neurophysiological deficits and is typically associated with rapid head accelerations common in sports-related incidents and automobile accidents. There are over 1.5 million TBIs in the United States each year, with children aged 0-4 being particularly vulnerable. TBI diagnosis is currently achieved through interpretation of clinical signs and symptoms and neuroimaging; however, there is increasing interest in minimally invasive fluid biomarkers to detect TBI objectively across all ages. Pre-clinical porcine models offer controlled conditions to evaluate TBI with known biomechanical conditions and without comorbidities. The objective of the current study was to establish pediatric porcine healthy reference ranges (RRs) of common human serum TBI biomarkers and to report their acute time-course after nonimpact rotational head injury. A retrospective analysis was completed to quantify biomarker concentrations in porcine serum samples collected from 4-week-old female (n = 215) and uncastrated male (n = 6) Yorkshire piglets. Subjects were assigned to one of three experimental groups (sham, sagittal-single, sagittal-multiple) or to a baseline only group. A rapid nonimpact rotational head injury model was used to produce mild-to-moderate TBI in piglets following a single rotation and moderate-to-severe TBI following multiple rotations. The Quanterix Simoa Human Neurology 4-Plex A assay was used to quantify glial fibrillary acidic protein (GFAP), neurofilament light (Nf-L), tau, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1). The 95% healthy RRs for females were calculated and validated for GFAP (6.3-69.4 pg/mL), Nf-L (9.5-67.2 pg/mL), and UCH-L1 (3.8-533.7 pg/mL). Rising early, GFAP increased significantly above the healthy RRs for sagittal-single (to 164 and 243 pg/mL) and increased significantly higher in sagittal-multiple (to 494 and 413 pg/mL) groups at 30 min and 1 h postinjury, respectively, returning to healthy RRs by 1-week postinjury. Rising later, Nf-L increased significantly above the healthy RRs by 1 day in sagittal-single (to 69 pg/mL) and sagittal-multiple groups (to 140 pg/mL) and rising further at 1 week (single = 231 pg/mL, multiple = 481 pg/mL). Sagittal-single and sagittal-multiple UCH-L1 serum samples did not differ from shams or the healthy RRs. Sex differences were observed but inconsistent. Serum GFAP and Nf-L levels had distinct time-courses following head rotations in piglets, and both corresponded to load exposure. We conclude that serum GFAP and Nf-L offer promise for early TBI diagnosis and intervention decisions for TBI and other neurological trauma.

Effect of Human Head Shape on the Risk of Traumatic Brain Injury: A Gaussian Process Regression-Based Machine Learning Approach.

Computational head injury models are promising tools for understanding and predicting traumatic brain injuries. However, most available head injury models are "average" models that employ a single set of head geometry (e.g., 50th-percentile U.S. male) without considering variability in these parameters across the human population. A significant variability of head shapes exists in U.S. Army soldiers, evident from the Anthropometric Survey of U.S. Army Personnel (ANSUR II). The objective of this study is to elucidate the effects of head shape on the predicted risk of traumatic brain injury from computational head injury models. Magnetic resonance imaging scans of 25 human subjects are collected. These images are registered to the standard MNI152 brain atlas, and the resulting transformation matrix components (called head shape parameters) are used to quantify head shapes of the subjects. A generative machine learning model is used to generate 25 additional head shape parameter datasets to augment our database. Head injury models are developed for these head shapes, and a rapid injurious head rotation event is simulated to obtain several brain injury predictor variables (BIPVs): Peak cumulative maximum principal strain (CMPS), average CMPS, and the volume fraction of brain exceeding an injurious CMPS threshold. A Gaussian process regression model is trained between head shape parameters and BIPVs, which is then used to study the relative sensitivity of the various BIPVs on individual head shape parameters. We distinguish head shape parameters into 2 types: Scaling components ${T_{xx}}$, ${T_{yy}}$, and ${T_{zz}}$ that capture the breadth, length, and height of the head, respectively, and shearing components (${T_{xy}},{T_{xz}},{T_{yx}},{T_{yz}},{T_{zx}}$, and ${T_{zy}}$) that capture the relative skewness of the head shape. An overall positive correlation is evident between scaling components and BIPVs. Notably, a very high, positive correlation is seen between the BIPVs and the head volume. As an example, a 57% increase in peak CMPS was noted between the smallest and the largest investigated head volume parameters. The variation in shearing components ${T_{xy}},{T_{xz}},{T_{yx}},{T_{yz}},{T_{zx}}$, and ${T_{zy}}$ on average does not cause notable changes in the BIPVs. From the Gaussian process regression model, all 3 BIPVs showed an increasing trend with each of the 3 scaling components, but the BIPVs are found to be most sensitive to the height dimension of the head. From the Sobol sensitivity analysis, the ${T_{zz}}$ scaling parameter contributes nearly 60% to the total variance in peak and average CMPS; ${T_{yy}}$ contributes approximately 20%, whereas ${T_{xx}}$ contributes less than 5%. The remaining contribution is from the 6 shearing components. Unlike peak and average CMPS, the VF-CMPS BIPV is associated with relatively evenly distributed Sobol indices across the 3 scaling parameters. Furthermore, the contribution of shearing components on the total variance in this case is negligible. Head shape has a considerable influence on the injury predictions of computational head injury models. Available "average" head injury models based on a 50th-percentile U.S. male are likely associated with considerable uncertainty. In general, larger head sizes correspond to greater BIPV magnitudes, which point to potentially a greater injury risk under rapid neck rotation for people with larger heads.

Rate of Initial Optic Nerve Head Capillary Density Loss and Risk of Visual Field Progression

Rapid initial optic nerve head capillary density loss may be used to assess the risk of glaucoma visual field progression. To investigate the association between the rate of initial optic nerve head capillary density loss from optical coherence tomography angiography (OCTA) and visual field progression. This was a retrospective study of a longitudinal cohort at a glaucoma referral center. A total of 167 eyes (96 with primary open-angle glaucoma and 71 with glaucoma suspect) of 109 patients were monitored for a mean (SD) of 5.7 (1.4) years from January 2015 to December 2022. Data analysis was undertaken in April 2023. The rates of initial capillary density and average retinal nerve fiber layer loss were calculated from the first 3 optic nerve head OCTA and OCT scans, respectively, during the initial follow-up (mean [SD], 2.0 [1.0] years). Based on the median rate, eyes were categorized into fast and slow progressor groups. The association between initial capillary density change or retinal nerve fiber layer thinning and visual field progression was evaluated using linear-mixed and time-varying Cox models. A total of 167 eyes of 109 patients (mean [SD] age, 69.0 [11.1] years; 56 [51.4%] female and 53 [48.6%] male) were assessed. Eighty-three eyes were slow OCTA progressors, while 84 eyes were fast with mean capillary density loss of -0.45% per year and -1.17% per year, respectively (mean difference, -0.72%/year; 95% CI,-0.84 to -0.60; P < .001). Similarly, 83 eyes were slow OCT progressors, while 84 eyes were fast with mean retinal nerve fiber layer thinning of -0.09 μm per year and -0.60 μm per year, respectively (mean difference, -0.51 μm/year; 95% CI,-0.59 to -0.43; P < .001). The fast OCTA and OCT progressors were associated with more rapid visual field loss (mean difference, -0.18 dB/year; 95% CI,-0.30 to -0.06; P = .004 and -0.17 dB/year; 95% CI,-0.29 to -0.06; P = .002, respectively). Fast OCTA progressing eyes were more likely to have visual field progression (hazard ratio, 1.96; 95% CI, 1.04-3.69; P = .04). Seventeen of 52 eyes (32.7%; 95% CI, 32.5-32.8) with fast OCTA and OCT progression developed subsequent visual field likely progression. Rapid initial optic nerve head capillary density loss from OCTA was associated with a faster rate of visual field progression and a doubling of the risk of developing event progression in this study. These findings may support clinical use of OCTA and OCT optic nerve head measurements for risk assessment of glaucoma progression.

Rapid brain MRI for image-guided ventricular catheter placement in pediatric patients: protocol and preliminary clinical outcomes.

Neuronavigation is a useful adjunct for catheter placement during neurosurgical procedures for hydrocephalus or ventricular access. MRI protocols for navigation are lengthy and require sedation for young children. CT involves ionizing radiation. In this study, the authors introduce the clinical application of a 1-minute rapid MRI sequence that does not require sedation in young children and report their preliminary clinical experience using this technique in their pediatric population. All patients who underwent ventricular catheter placement at a children's hospital using a rapid noncontrast MRI protocol, standard MRI, or head CT from July 2021 to August 2023 were included. Type of procedure, etiology of hydrocephalus, ventricle configuration and size, morphology of ventricles, need for adjunctive intraoperative ultrasound, duration of procedure, accuracy of catheter placement, and need for proximal revision within 90 days were retrospectively recorded and compared across imaging modalities. Sixty-eight patients underwent 83 procedures: 21 underwent CT navigation, 29 standard MRI, and 33 rapid MRI. Patients who received standard MRI more often had tumor etiology, while those who underwent CT and rapid MRI had posthemorrhagic etiology (χ2 = 13.04, p = 0.042). Intraoperative ultrasound was required for 1 patient in the standard MRI group and 1 patient in the CT group. There was no difference in procedure time across groups (p = 0.831). On multivariable analysis, procedure time differed by procedure type, where external ventricular drain placement and proximal revision were faster (p < 0.001 and p < 0.028, respectively). Proximal revision due to obstruction within 90 days occurred in 3 cases (in the same patient with complex loculated hydrocephalus) in the rapid MRI group and 2 cases in the CT group. Although this study was not powered for statistical inference, the authors report on the clinical use of a 1-minute rapid MRI sequence for neuronavigation in hydrocephalus or ventricular access surgery. There were no instances in which intraoperative ultrasound was required as an adjunct for procedures navigated with rapid MRI, and intraoperative time did not differ from that of standard navigation protocols.

Research on the Digital Preservation of Intangible Cultural Heritage of Folk Dance Art Category

Abstract In this paper, based on the rapid head generation technique of the model library, we obtain a frontal 2D face photo, mark 13 feature points selected from 7 parts, such as both eyes, nose, mouth, etc., to determine the approximate position of the whole facial features, simulate the real color of the face according to the texture mapping of the face, and at the same time, we add the texture features of the target face in the to the matching model, to achieve the mapping of overlaying texture to the neutral texture and the fusion of skin color. Using HigherHRNet network extraction to obtain the coordinate information of the joint points of the intangible cultural heritage dance inheritors and their heat maps, the obtained key frames of the dance features are connected in a certain order to obtain the synthesized folk dance video with gesture estimation. Combining semantic segmentation of keyframes and style rendering, the visual image of the dance is designed, and the intangible cultural heritage of folk dance is analyzed through examples. The results show that this paper’s method achieves more than 90% recognition accuracy on all three datasets and more than 94.8% recognition accuracy on the folk dance movement dataset. On the evaluation of folk dance movements, the average distance calculated by this paper’s algorithm is the largest, 95.7, and the average score is the lowest, 43.6. The average distance and average score of this paper’s algorithm are in between the above two cases, i.e., the experimental results verify the effectiveness of this paper’s method. This study promotes the intelligent protection and creative inheritance of Chinese non-heritage dances through digital protection.

The "Near"-Narrowed Internal Auditory Canal Syndrome in Adults: Clinical Aspects, Audio-Vestibular Findings, and Radiological Criteria for Diagnosis.

Vestibular Paroxysmia (VP) refers to short attacks of vertigo, spontaneous or triggered by head movements, and implies the presence of a compressive vascular loop in contact with the cochleovestibular nerve (CVN). Classically, a narrowed internal auditory canal (IAC) corresponds to a diameter of less than 2 mm on CT, usually associated with a hypoplastic CVN on MRI. The aim of this study was to discuss a distinct clinical entity mimicking VP in relation to a "near"-narrowed IAC (NNIAC) and to propose radiological criteria for its diagnosis. Radiological measurements of the IAC were compared between three groups: the study group (SG, subjects with a clinical presentation suggestive of VP, but whose MRI of the inner ear and pontocerebellar angle excluded a compressive vascular loop) and two control groups (adult and children) with normal vestibular evaluations and no history of vertigo. 59 subjects (18 M and 41 F) were included in the SG. The main symptoms of NNIAC were positional vertigo, exercise- or rapid head movements-induced vertigo, and dizziness. The statistical analysis in the study group showed that the threshold values for diagnosis were 3.3 mm (in tomodensitometry) and 2.9 mm (in MRI) in coronal sections of IAC. Although a significantly lower mean value for axial IAC diameter was found in SG compared with controls, the statistics did not reveal a threshold due to the large inter-individual variations in IAC measurements in normal subjects. There was no significant difference in IAC diameter between the adult and pediatric controls. In the present study, we report a new anatomopathological condition that appears to be responsible for a clinical picture very similar-but not identical-to VP in association with the presence of an NNIAC. The diagnosis requires a careful analysis of the IAC's shape and diameters in both axial and coronal planes.

Vestibular-evoked myogenic potentials and video head impulse test in cochlear otosclerosis

BackgroundOtosclerosis is one of the most common causes of hearing loss in adults with clinical onset between 20 and 40 years of age. Vestibular symptoms may be the most agonizing and primary symptom in cases with otosclerosis, so the assessment of patients is important. The vestibular-evoked myogenic potentials test (VEMP) is used to assess the saccular and the utricular functions using cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP), respectively. The video head impulse test (vHIT) which measure vestibulo-ocular reflex (VOR) to rapid impulsive head acceleration in the plane of each semicircular canal (SCC) has allowed quantitative monitoring of each canal function.MethodsTwenty subjects with bilateral otosclerosis were studied, ranging in age from 30 to 55 years, divided into two groups. One group consisted of 10 adult patients with bilateral conductive otosclerosis. The second group consisted of 10 adult patients with bilateral mixed otosclerosis. All the patients underwent cVEMP and oVEMP, using a BC 500Hz tone burst stimulus and vHIT in three planes, left anterior right posterior (LARP), right anterior left posterior (RALP), and lateral SCCs.ResultsThe findings indicate statistically significant differences in the peak-to-peak amplitudes of cVEMP and oVEMP in the two studied groups, and the mixed cases had lower amplitudes than conductive cases and a significant increase in p13 latencies. Also, there is a statistically significant difference in the lateral SCC gain between the two groups, as mixed cases had lower gain than conductive cases, but not for anterior or posterior SCCs, with no gain less than 0.8 in all three canals.ConclusionThe findings suggested that the saccule is more liable to be affected by cochlear otosclerosis followed by the utricle. The three SCCs are mostly spared.

Cervico-Ocular and Vestibulo-Ocular Reflexes in Subclinical Neck Pain and Healthy Individuals: A Cross-Sectional Study.

Alterations in neck sensory input from recurrent neck pain (known as subclinical neck pain (SCNP)) result in disordered sensorimotor integration (SMI). The cervico-ocular (COR) and vestibulo-ocular (VOR) reflexes involve various neural substrates but are coordinated by the cerebellum and reliant upon proprioceptive feedback. Given that proprioception and cerebellar processing are impaired in SCNP, we sought to determine if COR or VOR gain is also altered. COR and VOR were assessed using an eye-tracking device in 20 SCNP (9 M and 11 F; 21.8 (SD = 2.35) years) and 17 control (7 M and 10 F; 22.40 (SD = 3.66) years) participants. COR gain (10 trials): A motorized chair rotated the trunk at a frequency of 0.04 Hz and an amplitude of 5° while participants gazed at a circular target that disappeared after three seconds. VOR gain (30 trials): Rapid bilateral head movements away from a disappearing circular target while eyes fixated on the last observed target. Independent t-tests on COR and VOR gain were performed. SCNP had a significantly larger COR gain (p = 0.006) and smaller VOR gain (p = 0.487) compared to healthy controls. The COR group differences suggest an association between proprioceptive feedback and SMI, indicating COR may be a sensitive marker of altered cerebellar processing.

Repeated mild traumatic brain injury causes sex-specific increases in cell proliferation and inflammation in juvenile rats

Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated-mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long-Evans rats. We found that r-mTBI did not lead to cumulative neurological deficits with the model. R-mTBI animals exhibited an increase in BrdU + (bromodeoxyuridine positive) cells in the dentate gyrus (DG), and that this increase was more robust in male animals. This increase was not sustained, and cell proliferation returning to normal by PID3. A greater increase in BrdU + cells was observed in the dorsal DG in both male and female r-mTBI animals at PID1. Using Ki-67 expression as an endogenous marker of cellular proliferation, a robust proliferative response following r-mTBI was observed in male animals at PID1 that persisted until PID3, and was not constrained to the DG alone. Triple labeling experiments (Iba1+, GFAP+, Brdu+) revealed that a high proportion of these proliferating cells were microglia/macrophages, indicating there was a heightened inflammatory response. Overall, these findings suggest that rapid head acceleration with the ACHI model produces an mTBI, but that the acute neurological deficits do not increase in severity with repeated administration. R-mTBI transiently increases cellular proliferation in the hippocampus, particularly in male animals, and the pattern of cell proliferation suggests that this represents a neuroinflammatory response that is focused around the mid-brain rather than peripheral cortical regions. These results add to growing literature indicating sex differences in proliferative and inflammatory responses between females and males. Targeting proliferation as a therapeutic avenue may help reduce the short term impact of r-mTBI, but there may be sex-specific considerations.

Vestibulo-ocular Reflex – A Narrative Review

The vestibulo-ocular reflex (VOR) causes movements of the eye that are intended to compensate for head and body movements so that vision remains stable on the retina. VOR helps to stabilize the retinal image by rotating the eyes to compensate for movements of the head. The VOR keeps us steady and balanced even though our eyes and head are continuously moving during the performance of actions. The VORs are driven by signals coming from vestibular labyrinths and use subcortical, short-latency pathways from vestibular afferents to the extraocular motor neurons. The relatively simple neural architecture of these reflexive responses, coupled with their stereotyped but adaptable nature, makes them ideal to understand simple sensorineural transformations. Without VOR, when an individual walks down the street, it is difficult to read signs or even recognize faces. Even an inaccurate VOR can result in a slip of visual image concerning photoreceptors, causing blurring of the images. If the VOR is injured, the retinal slip occurs which causes instability in gaze during rapid head movements. The disruption of the VOR results in oscillopsia and abnormal nystagmus. Oscillopsia causes blurred vision when the head is in motion and objects appear to jiggle and bounce as this object does not fix at one point in the retina. The objective of this review article is to discuss the anatomy of VOR with its bedside examinations, clinical implications, and management of VOR failure.

Cerebrospinal fluid levels of neuroinflammatory biomarkers are increased in athletes with persistent post-concussive symptoms following sports-related concussion

A sports-related concussion (SRC) is often caused by rapid head rotation at impact, leading to shearing and stretching of axons in the white matter and initiation of secondary inflammatory processes that may exacerbate the initial injury. We hypothesized that athletes with persistent post-concussive symptoms (PPCS) display signs of ongoing neuroinflammation, as reflected by altered profiles of cerebrospinal fluid (CSF) biomarkers, in turn relating to symptom severity. We recruited athletes with PPCS preventing sports participation as well as limiting work, school and/or social activities for ≥ 6 months for symptom rating using the Sport Concussion Assessment Tool, version 5 (SCAT-5) and for cognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Following a spinal tap, we analysed 27 CSF inflammatory biomarkers (pro-inflammatory chemokines and cytokine panels) by a multiplex immunoassay using antibodies as electrochemiluminescent labels to quantify concentrations in PPCS athletes, and in healthy age- and sex-matched controls exercising ≤ 2 times/week at low-to-moderate intensity. Thirty-six subjects were included, 24 athletes with PPCS and 12 controls. The SRC athletes had sustained a median of five concussions, the most recent at a median of 17 months prior to the investigation. CSF cytokines and chemokines levels were significantly increased in eight (IL-2, TNF-α, IL-15, TNF-β, VEGF, Eotaxin, IP-10, and TARC), significantly decreased in one (Eotaxin-3), and unaltered in 16 in SRC athletes when compared to controls, and two were un-detectable. The SRC athletes reported many and severe post-concussive symptoms on SCAT5, and 10 out of 24 athletes performed in the impaired range (Z < − 1.5) on cognitive testing. Individual biomarker concentrations did not strongly correlate with symptom rating or cognitive function. Limitations include evaluation at a single post-injury time point in relatively small cohorts, and no control group of concussed athletes without persisting symptoms was included. Based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last SRC in athletes with persistent post-concussive symptoms. Since an ongoing inflammatory response may exacerbate the brain injury these results encourage studies of treatments targeting the post-injury inflammatory response in sports-related concussion.

Neuronal somatic plasmalemmal permeability and dendritic beading caused by head rotational traumatic brain injury in pigs-An exploratory study.

Closed-head traumatic brain injury (TBI) is induced by rapid motion of the head, resulting in diffuse strain fields throughout the brain. The injury mechanism(s), loading thresholds, and neuroanatomical distribution of affected cells remain poorly understood, especially in the gyrencephalic brain. We utilized a porcine model to explore the relationships between rapid head rotational acceleration-deceleration loading and immediate alterations in plasmalemmal permeability within cerebral cortex, sub-cortical white matter, and hippocampus. To assess plasmalemmal compromise, Lucifer yellow (LY), a small cell-impermeant dye, was delivered intraventricularly and diffused throughout the parenchyma prior to injury in animals euthanized at 15-min post-injury; other animals (not receiving LY) were survived to 8-h or 7-days. Plasmalemmal permeability preferentially occurred in neuronal somata and dendrites, but rarely in white matter axons. The burden of LY+ neurons increased based on head rotational kinematics, specifically maximum angular velocity, and was exacerbated by repeated TBI. In the cortex, LY+ cells were prominent in both the medial and lateral gyri. Neuronal membrane permeability was observed within the hippocampus and entorhinal cortex, including morphological changes such as beading in dendrites. These changes correlated with reduced fiber volleys and synaptic current alterations at later timepoints in the hippocampus. Further histological observations found decreased NeuN immunoreactivity, increased mitochondrial fission, and caspase pathway activation in both LY+ and LY- cells, suggesting the presence of multiple injury phenotypes. This exploratory study suggests relationships between plasmalemmal disruptions in neuronal somata and dendrites within cortical and hippocampal gray matter as a primary response in closed-head rotational TBI and sets the stage for future, traditional hypothesis-testing experiments.

Altered Auditory and Visual Evoked Potentials following Single and Repeated Low-Velocity Head Rotations in 4-Week-Old Swine.

Auditory and visually evoked potentials (EP) have the ability to monitor cognitive changes after concussion. In the literature, decreases in EP are commonly reported; however, a subset of studies shows increased cortical activity after injury. We studied auditory and visual EP in 4-week-old female Yorkshire piglets (N = 35) divided into anesthetized sham, and animals subject to single (sRNR) and repeated (rRNR) rapid non-impact head rotations (RNR) in the sagittal direction. Two-tone auditory oddball tasks and a simple white-light visual stimulus were evaluated in piglets pre-injury, and at days 1, 4- and 7 post injury using a 32-electrode net. Traditional EP indices (N1, P2 amplitudes and latencies) were extracted, and a piglet model was used to source-localize the data to estimate brain regions related to auditory and visual processing. In comparison to each group's pre-injury baselines, auditory Eps and brain activity (but not visual activity) were decreased in sham. In contrast, sRNR had increases in N1 and P2 amplitudes from both stimuli. The rRNR group had decreased visual N1 amplitudes but faster visual P2 latencies. Auditory and visual EPs have different change trajectories after sRNR and rRNR, suggesting that injury biomechanics are an important factor to delineate neurofunctional deficits after concussion.

DETERMINATION AND SIMULTANEOUSLY QUANTIFICATION OF FIVE ORGANIC VOLATILE IMPURITIES USING HEAD SPACE GAS CHROMATOGRAPHY IN LEVOCLOPERASTINE FENDIZOATE ACTIVE PHARMACEUTICAL INGREDIENTS AND DOSAGE FORMS

Objectives: Organic chemical solvents are generally used during drug material synthesis, excipients, as well as in the drug product formulation. They are not acceptable in the finished product. Hence, the main objective of our work is development and validation of rapid, sensitive, and selective head space gas chromatography (GC-HS) method for the determination of five organic volatile impurities (OVI) (methanol, ethanol, dichloromethane, toluene, and benzene) in Levocloperastine Fendizoate active pharmaceutical ingredient (API) and commercial syrups. Methods: The method was developed using a thermal gradient elution program associated with a column having dimensions are ZB-624, 30 m × 0.53 mm × 3.0 μm with a flow rate of 3.0 mL/min and Nitrogen (N2) as a carrier gas. A flame ionization detector was used as a detector, and its temperature is at 250°C whereas the injector temperature is at 225°C. The total run time is 25.0 min. Results: The newly developed GC-HS method was validated by its specificity and selectivity system precision, and method precision, limit of detection and limit of quantification, linearity, accuracy, robustness, ruggedness, and solution stability as per International Council for Harmonization (ICH). Quantization limits for five impurities were 210 ppm for methanol, 350 ppm for ethanol, 42 ppm for dichloromethane, 62 ppm for toluene, and 0.4 ppm for benzene. Correlation coefficient values of linearity were higher than 0.995 for five OVI. The mean recoveries of five impurities were between 90% and 110%. Conclusion: We found good and accepted results as per ICH guidelines for all validated parameters for five OVI. Thus, the developed GC-HS method was suitable for the separation and quantification of five OVI in Levocloperastine Fendizoate API and commercial syrups at present.

Myelin degradation, axonal changes and expression trajectories of glial cells stimulated by rapid head insult in humans to estimate approximate time elapsed since trauma

BackgroundPost severe traumatic brain injury (sTBI), axonal alterations lead to myelin loss and its degeneration. In the recovery phase, numerous intermingled biochemical pathways involving complex inflammatory reactions cloud the understanding of this yet undiscerned process that also varies with agonal period. In cases with dubious histories, approximating the survival time can be challenging, and expression levels of characteristic markers may aid forensic experts in the same.MethodsThis exploratory study recruited 100 samples—68 sTBI, 22 non-TBI and 10 age- and sex-matched control samples. Male:female ratio was 87:13. Histochemical staining using H&E was used to characterize myelination pattern, and IHC of GFAP and CD-68 were performed to assess astroglial and microglial reactions with respect to survival time in specific sites.ResultAmong sTBI, non-TBI and control recruits, sTBI patients depicted significant myelination abnormalities, astroglial proliferation and microglial reaction and varying with survival time. Non-TBI and control samples depicted nearly similar profiles.ConclusionIn order to untangle the complex mesh of biochemical responses, nuanced research on individual factors (both pre- and post mortem) with regard to specific site and survival time are warranted. Standardizing experimental data and converting it into empirical data shall aid forensic experts in suggesting approximate agonal period.