Concussion-related visual memory and reaction time impairment in college athletes improved after osteopathic manipulative medicine: a randomized clinical trial.

CONTEXT: Concussion is an acute, transient disruption in brain function due to head injury. Previous studies suggest osteopathic manipulative medicine (OMM) improved recovery from concussion. OBJECTIVES: The hypothesis was that new-onset impairments (NOI) of neurological functions identified by Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) will improve more so after OMM than after concussion-education. METHODS: College athletes presenting to the outpatient academic healthcare center (AHCC) with concussion due to head injury within the preceding 2 weeks were recruited for this IRB-approved, randomized, single-blinded trial. Consented men and women were randomized into groups receiving two OMM treatments or two concussion-education sessions to control for social effects. Preseason, Baseline, ImPACT was compared to Post-Injury scores to determine NOI. Baseline, Post-Injury, and Post-Interventions ImPACTs were compared by analysis of variance (ANOVA, α≤0.05). Post-Injury correlations and mean changes in King-Devick (KD) scores were analyzed. RESULTS: Post-Injury NOI were found in 77.8% (14/18) men and 85.7% (6/7) women, including ImPACT subscore indices for verbal and visual memory, processing speed (PS), and reaction time (RT). Of those with NOI, mean visual memory recovered by 50.0% following one and by 104.9% (p=0.032) following two OMM treatments in men and by 82.8% (p=0.046) following one treatment in women. Following two interventions, the mean RT in men receiving OMM improved by 0.10 more than education (p=0.0496). The effect sizes of OMM were large (Cohen's d=1.33) on visual memory and small (Cohen's d=0.31) on RT. CONCLUSIONS: The NOI in visual memory and RT following concussion significantly improved in the OMM group compared to the education group. Integrating OMM utilizing physical exam and this treatment was a safe individualized approach in athletes with acute uncomplicated concussions. Further research is warranted to improve the utilization of OMM for individuals with concussion.

Preliminary Effects of Osteopathic Manipulative Medicine on Reactive Oxygen Species in Parkinson's Disease: A Randomized Controlled Pilot Study.

Context Parkinson's disease (PD) is the second most common neurodegenerative disorder and causes many clinical manifestations including bradykinesia, tremor, postural instability, and musculoskeletal stiffness. Neurodegeneration is commonly associated with oxidative stress. Oxidative stress has not been measured in PD in relation to the manual techniques used in Osteopathic Manipulative Treatment (OMT). Objective To investigate the effect of OMT on oxidative stress biomarkers in PD. Methods In this randomized non-blinded study, 32 PD subjects were separated by block randomization into counseling and OMT groups, receiving respective interventions twice a week for six weeks. The counseling arm received informative sessions while the OMT arm received a set treatment protocol. Biomarkers of oxidative stress, malondialdehyde (MDA), dityrosine (DT), 3-nitrotyrosine (3-NT), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 8-isoprostane were measured before and after the first session and at weeks three, six, and 10 (four weeks after conclusion of intervention). Results No significant changes were found in blood plasma levels of MDA, DT, 3-NT, or 8-OHdG during or after intervention compared to controls (p > 0.05). No significant changes were found in urine 8-OHdG or 8-isoprostane during or after intervention compared to controls (p > 0.05). Conclusion OMT used in this study did not significantly affect the chosen oxidative stress biomarkers, however many limitations of the study may have impeded possible findings.

Abnormal Foot Progression Angle Kinematics in Cervical Dystonia Improved After Osteopathic Manipulative Medicine: A Prospective Case Series.

Introduction Cervical dystonia (CD), a rare disorder, is the most common form of dystonia, a movement disorder. Impairments in activities of daily living and quality of life may result from chronic pain, perceived stigma, difficulty walking, and/or lack of control over movements. Studies of treatments for difficulty walking in CD have been inconclusive. Osteopathic manipulative medicine (OMM) has been used to improve gait biomechanics in other health conditions. Foot progression angle (FPA) while walking indicates functional gait abnormalities that increase the risk of knee injury and osteoarthritis. Objective The aim of this study is to test if five-weekly treatments using an OMM sequence designed for CD improved abnormal gait biomechanics in individuals with CD by identifying and addressing somatic dysfunctions. Methods In this prospective case series, independently ambulating individuals with CD symptom onset before the age of 40 years, not due to traumatic injury, were evaluated utilizing validated scales for severity (Toronto western spasmodic torticollis rating scale [TWSTRsI]) and symptoms affecting quality of life (Cervical Dystonia Impact Profile [CDIP-58]), physical examination, and FPA before and after five-weekly OMM treatments. Lower body joint range of motion and angles were captured in a clinical gait lab by nine cameras collecting three-dimensional Whole-body position data during three trials of one gait cycle at participant-selected walking speed. The FPA waveforms during the gait cycle were quantified by Vicon Nexus and Polygon applications. Pretreatment and posttreatment results were compared to established healthy gait waveforms and tested by repeated measures ANOVA (α=0.05). Results Pretreatment waveforms in CD had a mean 5.13° of excess FPA during gait cycle phases requiring lower-extremity pronation compared to previously published age-gender-matched healthy waveforms. There was 96% improvement in pronation after five treatments, with a mean 0.21° (p=0.041) of excess FPA. Mean TWSTRs and CDIP-58 scores improved. On physical examination, the rotational direction of C2 vertebrae was contralateral to neck muscle hypertonicity. Vertical sphenobasilar synchondrosis strains were present in those with anterotorticollis. Participants had ipsilateral anterolateral neck muscle and anterolateral abdominal wall muscle hypertonicity. All patients had pelvic somatic dysfunctions with left-side superior relative to right-side and restriction from lower-extremity pronation (i.e., supination dysfunctions). Conclusion The FPA was significantly improved after treatment. This OMM sequence was well tolerated and may be useful for improving gait kinematics in individuals with CD. Randomized, controlled, long-term studies are needed to determine effectiveness.

Gut Microbiome Changes with Osteopathic Treatment of Constipation in Parkinson's Disease: A Pilot Study.

INTRODUCTION: The gut microbiome appears to be predictive of Parkinson's disease (PD) with constipation. Chronic constipation frequently manifests prior to motor symptoms and impairs quality of life. An osteopathic manipulative medicine (OMM) sequence used physical exam assessment and manual treatment of neuromusculoskeletal dysfunctions pertinent to constipation in PD for this prospective ABA-design study, IRB-NYITBHS1065. The effects of 4 weekly treatments on the gut microbiome among men and women over 40 years old with chronic constipation and PD were investigated. Severity of PD was rated with the Movement Disorders Society-Unified PD rating scale (UPDRS) in six subjects with constipation. Also, the Bristol stool scale and questionnaires validated for constipation were administered for diagnosis, symptom severity, and quality of life during a 4-week control-period (A), 4-weekly OMM-treatments (B), and 2-weeks no-intervention (A). Biweekly stool samples were assessed for normalized microbiota abundance. RESULTS: The mean Bristol rating improved from type 2 (± 1) Pre-OMM to 3 (± 1; p = .167; d = 0.677) Post-OMM. Mean constipation severity significantly decreased (p = .010; d = 1.508) Post-OMM. Mean quality of life significantly improved (p = .041; d = 1.072) Post-OMM. The Pre-OMM mean number of families within the phylum Firmicutes decreased by 3 (p = .043; d = 1.177) Post-OMM. There were significant changes in the normalized abundance of phyla Actinobacteria (p = .040; d = 0.845) and Verrucomicrobia (p = .024; d = 0.675) as well as in genus Roseburia (p = .033; d = 1.109), Intestinimonas (p = .035; d = 0.627) and Anaerotruncus (p = .004) Post-OMM. CONCLUSION: The gut microbiome shifted among individuals with constipation and PD after four weekly treatments with the OMM-sequence. Changes in the gut microbiome Post-OMM were associated with UPDRS results and constipation measures. Clinical trials and studies to develop the gut microbiome into a validated biomarker for PD are necessary to understand the impact of OMM in patients with PD and constipation.

Cranial Strain Patterns Associated With Concussions.

CONTEXT: Concussions can cause cognitive impairment, somatic symptoms, and behavioral changes. Symptoms may vary in severity, depending on the degree of traumatic force. Due to the biomechanical nature of this trauma, cranial somatic dysfunctions may commonly be seen in patients with concussion. OBJECTIVE: To determine whether patients were more likely to have nonphysiologic cranial somatic dysfunctions than physiologic cranial somatic dysfunctions after sustaining a concussion. METHODS: College athletes who had a concussion based on the Immediate Post-Concussion Assessment and Cognitive test were evaluated by a physician within 1 week of the injury. Patients were evaluated for somatic dysfunctions of the cranium. Cranial somatic dysfunctions were documented; test scores and force vectors were compared with the type of strain pattern using SPSS, with P<.05 demonstrating statistical significance. RESULTS: Sixteen patients were included in the study: 10 with nonphysiologic cranial strain somatic dysfunctions and 6 with physiologic dysfunctions. Compared with lateral forces, forces of impact with anterioposterior vectors were associated 1.5 times more often with nonphysiologic rather than physiologic cranial somatic dysfunctions (P=.697). An analysis of specific cranial strain patterns and impact force vectors showed no statistical significance (P=.096). CONCLUSION: There was no statistically significant association showing that concussion patients were more likely to have nonphysiologic cranial somatic dysfunctions compared with physiological cranial somatic dysfunctions. However, nonphysiologic cranial somatic dysfunctions did show a trend toward association with concussion. Further studies are needed to better understand the potential association between concussion and cranial somatic dysfunctions.

Effectiveness of Osteopathic Manipulative Medicine vs Concussion Education in Treating Student Athletes With Acute Concussion Symptoms.

CONTEXT: Concussion, a type of mild traumatic brain injury, is a disruption in normal brain function due to head injury. New-onset symptoms from concussion vary, likely depending on the areas of the head and neck affected; they can be severe and debilitating. Current treatment options are limited and difficult to individualize. Osteopathic manipulative medicine (OMM) can aid musculoskeletal restrictions that can potentially improve concussion symptoms. OBJECTIVE: To assess concussion symptom number and severity in participants with concussion who received either OMM or an educational intervention. METHODS: A randomized controlled trial was conducted at the New York Institute of Technology Academic Health Care Center. Patients presenting to the center with concussion-like symptoms due to recent head injury within the previous 7 days provided consent and were randomized into 2 intervention groups, receiving either 1 OMM treatment (n=16) or 1 concussion education intervention (n=15). Participants were assessed before and after the intervention with the validated Symptom Concussion Assessment Tool fifth edition (SCAT-5) for quantification of number of symptoms and their severity. Collected data were analyzed using the Mann-Whitney U test and the repeated-measures analysis of variance. RESULTS: Thirty-one participants were enrolled in the study; after 1 control participant was excluded due to incomplete data, 30 patient records were analyzed. The OMM intervention group had a significant decrease in symptom number (P=.002) and symptom severity (P=.001) compared with the concussion education group. CONCLUSION: When used in the acute setting, OMM significantly decreased concussion symptom number and severity compared with concussion education. This study demonstrates that integration of OMM using a physical examination-guided, individualized approach is safe and effective in the management of new-onset symptoms of uncomplicated concussions. (Clinicaltrials.gov No. NCT02750566).

Effects of Osteopathic Manipulative Treatment on Sleep Quality in Student Athletes After Concussion: A Pilot Study.

CONTEXT: Impaired sleep quality is among many symptoms observed in patients with a concussion and may predispose a patient to a prolonged recovery course and a later return to their daily activities. Studies have suggested that osteopathic manipulative treatment (OMT) may play a role in improving sleep quality. OBJECTIVE: To investigate how OMT may play a role in the management and overall healing process in patients with a concussion by improving sleep quality. METHODS: Data were collected from a randomized, controlled study on OMT and concussion (of which this study represents 1 arm) to investigate the effects of OMT vs concussion education counseling on sleep quality in student athletes with a concussion. Student athletes with no medical history of neurodegenerative disease who presented to the New York Institute of Technology College of Osteopathic Medicine Academic Healthcare Center with a concussion following a sport-related injury were enrolled in the study. Participants received OMT intervention or standard counseling on how to care for a concussion during their first and second visits. Participants rated their symptoms, including sleep quality, on the validated scale Sport Concussion Assessment Tool 5th Edition at 3 consecutive visits during 1 week. The mean sleep quality score within and between the OMT and education groups before each of 2 interventions and at the third visit were compared and analyzed using the Mann-Whitney U test. RESULTS: Thirty participants were enrolled in the study. Total symptom data showed a stronger, significant correlation with sleep scores than with other symptoms. Participants receiving OMT (n=16) reported overall 80% and 76% improvement in sleep quality from pre-OMT values to their second and third visits, respectively. Participants who had an educational intervention (n=14) reported a 36% and 46% improvement from pre-OMT values to their second and third visits, respectively. CONCLUSION: The beneficial relationship trend between OMT and sleep quality in patients with a concussion was not statistically significant. Owing to the limitations of this study, further research with a larger population and sham control participants is warranted. (clinicaltrials.gov No. NCT02750566).

Effects of depression and exercise on health-related quality of life in patients with Parkinson's disease.

OBJECTIVES: There is limited literature describing the effect exercise may have on depression and an individual's health-related quality of life (HRQoL) in Parkinson's Disease (PD). We aim to quantify this effect. METHODS: A cross-sectional questionnaire was administered to 60 PD subjects. The Parkinson's Disease Questionnaire-39 (PDQ-39) summary index and the Geriatric Depression Scale-30 were used to quantify HRQoL and depression, respectively. Data were obtained on exercise habits. ANOVA and multivariate linear regression analysis were used to calculate mean differences in HRQoL. RESULTS: Depression was consistently related to HRQoL (p < 0.05). Of those who exercised as an adult before PD diagnosis, 49.02% (n = 25) reported depression as compared to 88.89% (n = 8) of those who did not report adult exercise (p = 0.03). Those who exercised frequently as an adult prior to PD diagnosis had a better PDQ-39 Cognitive Index (p = 0.03). Those who were not depressed and were currently exercising had a significantly higher HRQoL than those who were depressed and did not exercise (p < 0.01). DISCUSSION: Exercising and depression may interact to affect HRQoL. Thus, coordination of mental health evaluation and exercise regimens in persons with PD may improve HRQoL.

Integration of Osteopathic Manual Treatments in Management of Cervical Dystonia with Tremor: A Case Series.

BACKGROUND: Cervical dystonia, also known as spasmodic torticollis, is a chronic disorder in which patients exhibit involuntary repetitive contractions of neck muscles resulting in abnormal postures or movements. Occasionally, there is also a dystonic head tremor. The underlying mechanisms for cervical dystonia and dystonic tremor are not clear, and treatments are limited. CASE REPORT: In the present cases, two females with head tremor starting in adolescence developed worsening symptoms of cervical dystonia with dystonic tremor in their 60s. On osteopathic physical examination, both had a vertical type strain to the sphenobasilar synchondrosis. DISCUSSION: Vertical strains are more frequently found in patients after head trauma, congenital or later in life, than in healthy patients, and head trauma may have been a precipitating factor in these patients. There were improvements in cervical dystonia symptoms, including tremor, in both patients after osteopathic manual treatment.

Osteopathic manipulation as a complementary approach to Parkinson's disease: A controlled pilot study.

BACKGROUND: Osteopathic Manipulative Medicine (OMM) is a therapy of manual forces that is directed to improve function and homeostasis. It has been shown to improve balance in individuals with dizziness, and improve gait in Parkinson's disease (PD). This study was designed to determine if our pre-defined OMM protocol would improve motor function and balance in individuals with PD. METHODS: A randomized controlled trial to test OMM on balance and motor function in PD measured by the Mini-BESTest, Sensory Organization Test (SOT), and MDS-UPDRS. 11 Subjects (age 75±16) were randomly assigned to either bi-weekly OMM treatments first for 6 weeks or weekly counseling sessions from a medical provider for 6 weeks as a placebo-control. 9 subjects completed this study. RESULTS: There were no significant changes in SOT or Mini BESTest in either group (p < 0.05). There was significant improvement in the OMM group for MDS-UPDRS. CONCLUSIONS: Our pilot data showed OMM treatment bi-weekly for 6 weeks improved motor function. There were no significant changes in balance, however there were clinically relevant improvements after 6 weeks of OMM. Using a predefined protocol, OMM may be a complementary approach to improving balance and motor function in individuals with PD.

The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-ß and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

Methylmercury-Dependent Increases in Fluo4 Fluorescence in Neonatal Rat Cerebellar Slices Depend on Granule Cell Migrational Stage and GABAA Receptor Modulation.

Methylmercury (MeHg) disrupts cerebellar function, especially during development. Cerebellar granule cells (CGC), which are particularly susceptible to MeHg by unknown mechanisms, migrate during this process. Transient changes in intracellular Ca(2+) (Ca(2+) i) are crucial to proper migration, and MeHg is well known to disrupt CGC Ca(2+) i regulation. Acutely prepared slices of neonatal rat cerebellum in conjunction with confocal microscopy and fluo4 epifluorescence were used to track changes induced by MeHg in CGC Ca(2+) i regulation in the external (EGL) and internal granule cell layers (IGL) as well as the molecular layer (ML). MeHg caused no cytotoxicity but did cause a time-dependent increase in fluo4 fluorescence that depended on the stage of CGC development. CGCs in the EGL were most susceptible to MeHg-induced increases in fluo4 fluorescence. MeHg increased fluorescence in CGC processes but only diffusely; Purkinje cells rarely fluoresced in these slices. Neither muscimol nor bicuculline alone altered baseline fluo4 fluorescence in any CGC layer, but each delayed the onset and reduced the magnitude of effect of MeHg on fluo4 fluorescence in the EGL and ML. In the IGL, both muscimol and bicuculline delayed the onset of MeHg-induced increases in fluo4 fluorescence but did not affect fluorescence magnitude. Thus, acute exposure to MeHg causes developmental stage-dependent increases in Ca(2+) i in CGCs. Effects are most prominent in CGCs during development or early stages of migration. GABAA receptors participate in an as yet unclear manner to MeHg-induced Ca(2+) i dysregulation of CGCs.

Continuous exposure to low concentrations of methylmercury impairs cerebellar granule cell migration in organotypic slice culture.

Chronic, low-level perinatal exposure to methylmercury (MeHg) is associated with neurological and motor deficits that appear to result from cerebellar dysfunction. Neuropathological studies suggest that these deficits are due to impaired cerebellar granule cell (CGC) migration. Although neuronal migration in vivo and in vitro has been shown to be impaired during acute and/or high level exposure to MeHg, the cellular effects of chronic exposure to submicromolar and micromolar levels of MeHg during development are not clear. The majority of CGC migration in rats occurs between postnatal days 8 and 14 (P8 and 14); migration peaks on P10 and 11. Organotypic cultures of parasagittal slices of cerebellum from P8 rats were exposed to low levels of MeHg (0.2-5.0microM) for 3 or 7 days, and CGC viability and migration were assessed. MeHg-induced cell death was time- and concentration-dependent. After 3 days of exposure CGC viability decreased in 3microM MeHg and declined to 42.7% in 5microM MeHg. Cultures treated with MeHg for 7 days showed decreased CGC viability in 1microM MeHg, which declined to 62.8% in 3microM MeHg. CGC migration was assessed by BrdU pulse-chase labeling. Migration into the internal granule cell layer (IGL) was impaired in cultures exposed to >or=1microM MeHg for 3 days or >or=0.5microM for 7 days. CGCs failed to initiate migration from the external germinal cell layer at the same level of exposure. For those cells which initiated migration, MeHg reduced the number that migrated into the IGL. This implied a slowing of migration once it had begun. These effects occurred with no overall change in cerebellar cortical structure, or loss of granule cell viability. Thus, chronic exposure to low micromolar concentrations of MeHg impairs development of the cerebellar cortex in a slice culture model.

The NR2B subunit in NMDA receptors is functionally important during cerebellar granule cell migration.

Migration of cerebellar granule cells (CGCs) from the external germinal cell layer (EGL) to the internal granule cell layer (IGL) within the cerebellar cortex is a crucial developmental process. Antagonists to NMDA receptors impair CGC migration significantly, but studies to determine which subunit subtypes control or affect migration have been controversial. Migrating CGCs transiently express NMDA receptor subunit subtypes NR1a plus NR2B. Grafted NR1-/- subunit knockout cells continue to migrate, indicating that the NR1 subunit is not necessary for migration. In the present study, the functional importance of the NR2B subtype in developing cerebellum was investigated using organotypic slice cultures prepared from postnatal day 8 (P8) rats. Slice cultures were labeled with bromodeoxyuridine (BrdU) during the first 20h and then continuously treated with the NR2B-subtype-specific NMDA antagonist, ifenprodil, or the non-specific NMDA antagonist, APV, for 7 days. Cultures were incubated with fluorescently tagged anti-BrdU IgG and the percent of BrdU-labeled CGCs that migrated from the EGL to the IGL during treatment was analyzed using laser confocal microscopy. Migration into the IGL was significantly impaired by treatment with 0.5 and 1.0 microM ifenprodil. Fewer cells had migrated to the IGL in 1.0 microM ifenprodil than in 0.5 microM ifenprodil; there was no significant difference between the percent impairment caused by 1.0 microM ifenprodil and 50 microM APV. Untreated controls had few, if any, CGCs in the EGL at DIV 8. The percent of CGCs remaining in the EGL following treatment with antagonists significantly increased, indicating impairment of migration. In conclusion, the NR2B subunit appears to be necessary for CGC migration.