Parkinson’s Disease and Forced Exercise: A Preliminary Study

Objective. The concept of forced exercise has drawn attention for the treatment of Parkinson’s disease symptoms with anecdotal reports of success. This study sought to ascertain any significant effect of forced exercise using a motorized stationary bicycle when compared to controls on Parkinson’s disease symptoms in a blinded, randomized, and controlled setting. Setting. Parkinson’s disease outpatient clinic, Veterans Administration Medical Center. Method. We assessed 23 patients (13 experimental and 10 controls) on a number of standard Parkinson’s measures at baseline, after participation in eight weeks of twice weekly forced exercise or eight weeks of conventional clinic care, and then after a three-month period had elapsed. Dependent measures were UPDRS-III, Berg Balance Scale, finger taping test, and the PDQ-39. Results. Results did not demonstrate any main effect differences between the exercise and control groups on any measure at any point in time. A within subjects effect was demonstrated for the forced exercise group on overall UPDRS-III scores at the three-month end point. No other within group effects were noted. Results suggest that early enthusiasm for forced exercise may need tempering. Limitations of the study are discussed as well as numerous logistical challenges to this type of study

Differential Eye Movements in Mild Traumatic Brain Injury vs. Normal Controls

Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly and field ready technique to meet this need. Eye tracking data collected via a head mounted, video-based binocular eye tracker was used to examine saccades, fixations and smooth pursuit movement in 60 military Service Members with post concussive syndrome (PCS) and 26 asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified. The diagnosis of mTBI was confirmed by the study physiatrist’s history, physical examination, and a review of any medical records. Results demonstrated that subjects with symptomatic mTBI had statistically larger position errors, smaller saccadic amplitudes, smaller predicted peak velocities, smaller peak accelerations, and longer durations. Subjects with symptomatic mTBI were also less likely to follow a target movement (less primary saccades). In general, symptomatic mTBI tracked the stepwise moving targets less accurately, revealing possible brain dysfunction. A reliable, standardized protocol that appears to differentiate mTBI from normals was developed for use in future research. This investigation represents a step toward objective identification of those with PCS. Future studies focused on increasing the specificity of eye movement differences in those with PCS are needed

Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury

The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (mTBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between- and within-groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mTBI when compared with a sham-control

Post-acute Brain Injury Urinary Signature: A New Resource for Molecular Diagnostics

Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress particularly in cerebrospinal fluid with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop in part due to restricted and intermittent barrier access. Further, a greater number of molecular variables may be required to inform on patient status given the multifactorial nature of brain injury. Presented is an alternative approach profiling peripheral fluid for a class of small metabolic by-products rendered by ongoing brain pathobiology. Urine specimens were collected for head trauma subjects upon admission to acute brain injury rehabilitation and nontraumatized matched controls. An innovative data-independent mass spectrometry approach was employed for reproducible molecular quantification across osmolarity-normalized samples. The postacute human traumatic brain injury urinary signature encompassed 2,476 discriminant variables reproducibly measured in specimens for subject classification. Multiple sub-profiles were then discerned in correlation with injury severity per Glasgow Comma Scale and behavioral and neurocognitive function per Patient Competency Rating Scale and Frontal Systems Behavioral Scale. Identified peptide constituents were enriched for outgrowth and guidance, extracellular matrix and post-synaptic density proteins, which were reflective of ongoing post-acute neuroplastic processes demonstrating pathobiological relevance. Taken together, these findings support further development of diagnostics based on brain injury urinary signatures using either combinatorial quantitative models or patternrecognition methods. Particularly, these findings espouse assay development to address unmet diagnostic and theragnostic needs in brain injury rehabilitative medicine

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

Most traumatic brain injuries (TBIs) during military deployment or training are clinically “mild” and frequently caused by non-impact blast exposures. Experimental models were developed to reproduce the biological consequences of high-intensity blasts causing moderate to severe brain injuries. However, the pathophysiological mechanisms of low-intensity blast (LIB)-induced neurological deficits have been understudied. This review provides perspectives on primary blast-induced mild TBI models and discusses translational aspects of LIB exposures as defined by standardized physical parameters including overpressure, impulse, and shock wave velocity. Our mouse LIB-exposure model, which reproduces deployment-related scenarios of open-field blast (OFB), caused neurobehavioral changes, including reduced exploratory activities, elevated anxiety-like levels, impaired nesting behavior, and compromised spatial reference learning and memory. These functional impairments associate with subcellular and ultrastructural neuropathological changes, such as myelinated axonal damage, synaptic alterations, and mitochondrial abnormalities occurring in the absence of gross- or cellular damage. Biochemically, we observed dysfunctional mitochondrial pathways that led to elevated oxidative stress, impaired fission-fusion dynamics, diminished mitophagy, decreased oxidative phosphorylation, and compensated cell respiration-relevant enzyme activity. LIB also induced increased levels of total tau, phosphorylated tau, and amyloid β peptide, suggesting initiation of signaling cascades leading to neurodegeneration. We also compare translational aspects of OFB findings to alternative blast injury models. By scoping relevant recent research findings, we provide recommendations for future preclinical studies to better reflect military-operational and clinical realities. Overall, better alignment of preclinical models with clinical observations and experience related to military injuries will facilitate development of more precise diagnosis, clinical evaluation, treatment, and rehabilitation

Caregiver distress in parkinsonism

This study examined the frequency and degree of caregiver burden in persons with parkinsonism, a group of disorders with four primary symptoms that include tremor, rigidity, postural instability, and bradykinesia. We assessed associations between perceived caregiver burden and physical, cognitive, and functional impairments using well-established tools for persons with parkinsonism. The 49 individuals with parkinsonism ranged in age from 61 to 87 (mean = 75), while their caregivers (N = 49) ranged in age from 48 to 83 (mean = 70). The caregivers were predominantly either wives (82%) or daughters (6%), with other family members, friends, and/or neighbors (12%) making up the rest. The caregivers reported a relatively high ability for coping (mean scores = 4.6/6). Caregiver burden was significantly negatively associated with activities of daily living and motoric difficulties as measured on the Unified Parkinson\u27s Disease Rating Scale (UPDRS). Likewise, caregiver burden was negatively associated with caregiver self-reported sleep and coping ability. Results did not demonstrate an association on the UPDRS among mentation, behavior, and mood. We found a significant negative correlation for mentation between the Folstein Mini-Mental Status Examination and caregiver burden measures; however, we did not find this association with the Dementia Rating Scale-2. Patient\u27s self-reported pain and caregiver burden were not associated

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p