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.

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.

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.

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.