This review explores the pivotal role of the brainstem in regulating gait, highlighting its function in modulating the balance between rhythmic motor patterns and goal-directed behaviors. Gait is a voluntary motor behavior that involves the continuous interplay of rhythmic motor control and higher-order cognitive processes. Key brainstem structures, including the pedunculopontine nucleus (PPN), dorsal raphe nucleus (DRN), and gigantocellular nucleus (GiN), integrate sensory inputs, motivational states, and contextual cues to modulate locomotion. These nuclei maintain efficient motor adaptation and conserve cognitive resources by coordinating brainstem and spinal cord circuitry (i.e., central pattern generators) which "automate" the control of muscles that produce the rhythmical locomotor behaviors. While this review primarily focuses on these three key nuclei, it also briefly discusses additional brainstem structures involved in gait and postural control, such as the vestibular nuclei, red nucleus, and inferior olive. Disruptions in the brainstem networks due to neurodegenerative diseases like Parkinson's disease and aging impair the ability to adjust the level of cognitive control required for gait, necessitating increased cognitive effort for motor and balance regulation. By presenting a hierarchical model of gait control, this review provides insight into the dynamic interplay between brainstem, spinal pattern generators, and cortical systems in locomotion control.

Background: Although care of Parkinsonism (PKM) is assumed to be optimally provided by movement disorder neurologists within an interdisciplinary clinic model, there is a paucity of published data to support this. Objectives: To investigate the impact of movement disorder neurologist care of individuals with Parkinsonism (PKM). Methods: A retrospective exposure design was adopted using administrative data. Incident PKM individuals were identified in billing claims. A nine-year exposure period to movement disorder neurologist, general neurologist and non-neurologist care was calculated based on the billing codes. Regression models were used to test the association of provider exposure on time to death and long-term care (LTC) admission. Linear models were used to test varying provider exposure and hospital admissions, hospital days and emergency department visits. Results: 1914 incident individuals were identified. There was no difference in PKM mortality, emergency visits, hospital admissions, or hospital days between providers, however exposure to general neurology and nonneurology care was associated with a significantly higher risk of admission to LTC compared to movement disorder neurologist care (HR 1.43; 95% CI 1.09 -1.87 for general neurology (p -value = 0.0089); HR 1.61; 95% CI 1.25 -2.05 for non-neurology (p -value = 0.0002), respectively. Conclusion: Movement disorder neurologist care is associated with a lower risk of admission to LTC over general neurologist care in individuals with PKM.

APPENDIX S1. Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND AND PURPOSE Gait impairment is a hallmark of Parkinson's disease (PD). Natural walking involves more cognitive demand than treadmill walking or in-laboratory walking tests because patients have to actively work on navigation and top-down cognitive control which taxes cognitive reserve in the prefrontal cortex. To mimic the prefrontal engagement occurring with natural walking in a controlled and safe environment, dual-task (DT) treadmill walking has been developed. In this study, we tested the feasibility of imaging DT walking-related changes in brain glucose metabolism in patients with PD. METHODS Fifteen patients with PD were scanned with fluorodeoxyglucose (FDG) positron emission tomography. Five patients performed DT walking, and 10 patients were rested during the FDG uptake period. First, the images were contrasted between the groups. Second, the walking-related brain glucose metabolism was inspected at the individual level. RESULTS Consistently increased glucose metabolism was identified in DT walking versus rest in the primary visual/sensorimotor areas, thalamus, superior colliculus, and cerebellum. In individual level analysis, patients with less progressed disease (n = 3) showed prefrontal activity during DT walking while patients with more progressed disease (n = 2) did not. CONCLUSION This study confirms the feasibility of imaging glucose metabolism during DT walking in patients with PD. We also report that during DT walking, there is a lesser degree of prefrontal engagement in the patients with more progressed disease compared to those with less progressed disease, implying increased degrees of frontal dysfunction with PD progression.

Balance and gait impairments, and consequently, mobility restrictions and falls are common in Parkinson’s disease (PD). Various cognitive deficits are also common in PD and are associated with increased fall risk. These mobility and cognitive deficits are limiting factors in a person’s health, ability to perform activities of daily living, and overall quality of life. Community ambulation involves many dual-task (DT) conditions that require processing of several cognitive tasks while managing or reacting to sudden or unexpected balance challenges. DT training programs that can simultaneously target balance, gait, visuomotor, and cognitive functions are important to consider in rehabilitation and promotion of healthy active lives. In the proposed multi-center, randomized controlled trial (RCT), novel behavioral positron emission tomography (PET) brain imaging methods are used to evaluate the molecular basis and neural underpinnings of: (a) the decline of mobility function in PD, specifically, balance, gait, visuomotor, and cognitive function, and (b) the effects of an engaging, game-based DT treadmill walking program on mobility and cognitive functions. Both the interactive cognitive game tasks and treadmill walking require continuous visual attention, and share spatial processing functions, notably to minimize any balance disturbance or gait deviation/stumble. The ability to “walk and talk” normally includes activation of specific regions of the prefrontal cortex (PFC) and the basal ganglia (site of degeneration in PD). The PET imaging analysis and comparison with healthy age-matched controls will allow us to identify areas of abnormal, reduced activity levels, as well as areas of excessive activity (increased attentional resources) during DT-walking. We will then be able to identify areas of brain plasticity associated with improvements in mobility functions (balance, gait, and cognition) after intervention. We expect the gait-cognitive training effect to involve re-organization of PFC activity among other, yet to be identified brain regions. The DT mobility-training platform and behavioral PET brain imaging methods are directly applicable to other diseases that affect gait and cognition, e.g., cognitive vascular impairment, Alzheimer’s disease, as well as in aging.

Mild cognitive impairment (MCI) is common in Parkinson’s disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson’s patients. We recruited 18 Parkinson’s disease patients—10 PDNC [normal cognition Parkinson’s disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson’s disease; MoCA < 26) —and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer’s disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson’s patient groups, but not in healthy control subjects. Interestingly, PDNC’s functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer’s disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson’s disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson’s disease. Our findings support and complement the dual syndrome hypothesis.

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p= 0.003) and Week 8 (p= 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p= 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.

In 1908, Wilson1 reported observations of associated ear and eye movements in 50 normal persons, later called the “oculo-aural phenomenon of Wilson.”2 He specifically described that 40% of people demonstrated a backward curling of the either one or both pinnae associated with voluntary lateral eye movements. He recognized the transverse auricular muscle (TAM) as responsible for this movement. We present herein an, as yet, unreported oculo-auricular synkinesia post–facial palsy, while providing evidence to support a predominantly ipsilateral connection subserving Wilson's phenomenon and confirming additional involvement of the superior auricular muscle. This 28-year-old male, with a lifelong ability to wiggle his ears, developed a complete, right, facial palsy at age 16 without vertigo, change in facial sensation, taste, balance, or hearing. He had marked recovery within 1 month. By age 24, noted sequelae included a pulling sensation (without observed movement) of the right face and ear, along with orbicularis oculi myokymia and mild facial synkinesia. By age 26, he noted right ear movement while smiling and chewing. He also had developed crocodile tears when eating. By age 28, there was further progression in his symptoms with a more asymmetric smile with greater elevation of the mouth on the right. His right ear felt “as if there was a 10-pound dumbbell attached to the ear constantly weighing it down.” The ear did not visibly move in association with this sensation. On examination, he could still independently and prominently wiggle either ear. He had a greater sensory perception of ear movement on the right. There was no weakness of the face, and ocular apertures were equal. There was subtle exaggeration of smiling on the right. After relaxation, subsequent to forceful eye closure, there were brief myokymic twitches of the orbicularis oculi. Facial sensation and corneal reflexes were intact. As seen in Video 1, with smiling, the right ear, but not the left, retracted. With gaze to the left, there was clear movement of the right pinna. Specifically, ear movement began with activation of the superior auricular muscle (SAM), resulting in ear elevation followed by posterior displacement of the concha rim attributable to posterior auricular muscle contraction (PAM), and finally the TAM retracted the upper ear. Gaze to the right did not trigger movement in either ear. No left ear movement was evident on any gaze. There was movement of the right ear with head rotation to the left, but no movement of the left ear with head turning to the right. Right ear synkinetic movement was evident with broad smiling, head turning to the left, and chewing, but not with convergence, spontaneous blinking, forehead wrinkling, tight eye closure, and down- or upgaze (Video 2). The patient reported a sensation of right, but not left, ear movement with convergence and swallowing, although this is not seen in the video. Few humans are able to voluntarily move their ears. Ear wiggling ability appears to have become useless to our survival, and evolutionary events have rendered it a vestigial or fictive motor system.3, 4 The innate neural networks subserving auricular movement remain a topic of research. They are being explored as a clinical sign, when absent5 or present. They help understand mechanisms of neuroplasticity in association with facial palsy4, 6 and identifying details of poorly defined brainstem pathways.7 Involuntary movements involving muscles innervated by the facial nerve are recognized complications of Bell's palsy. These include: facial muscle contractures, muscle tone increase, muscle spasms, myokymic discharges, and synkinesia.6 Synkinesia occurs in up to 16% of cases and involves muscles of the eye (oral-ocular), cheek, mouth (oculo-oral), and, less commonly, the forehead.8, 9 Explanations include aberrant reinnervation, ephaptic transmission, brainstem reflex reorganization, hyperexcitability of facial nucleus motor neurons, and changes in interneuronal excitability.9-11 Although neurophysiological recordings confirm auricular synkinetic electromyography (EMG) activity in association with lateral gaze, yawning, talking, swallowing, and breathing,4, 6 we have been unable to find any previously published report of a unilateral, observable, ocular-auricular synkinetic movement as a consequence of facial palsy or hemifacial spasm. Wilson's phenomenon (oculo-auricular phenomenon)1 is a normal phenomenon and consists of the bilateral, synkinetic contraction of the TAM during strong lateral gaze.7 This phenomenon was evident using EMG in 24 of 25 normal controls and was stronger in the ear the eyes were directed away from.7 Convergence also triggers the phenomenon. Urban et al.7 concluded that the connections subserving this descend from the superior colliculus uncrossed to the ipsilateral facial nucleus, as well as descending and crossing in the mid pons to the contralateral facial nucleus. Patuzzi et al.12 found that responses were larger ipsilateral, rather than contralateral, to the direction of gaze. This case uniquely demonstrates a manifest ear synkinesia and, more specifically, a unilateral ocular-auricular synkinetic movement post–Bell's palsy. The mechanism (see Fig. 1) is assumed to relate to a hyperexcitability of the facial nucleus motor neurons, allowing an unmasking or coactivation of auricular muscles with voluntary gaze to the opposite side. This supports the predominant anatomical connection from the superior colliculus being ipsilateral in this case, given that gaze toward the right ear caused no evident left ear movement. This also provides evidence to support hyperexcitability at a facial nuclear level as an explanation for post–facial palsy synkinesia as opposed to previous explanations of aberrant fiber regeneration or ephaptic transmission.11 The late appearance of synkinesia in our case is hard to explain. A steady state of recovery is expected by 1 year post–facial palsy.13 Synkinesia is more common after facial palsy, but it has also been reported in hemifacial spasms.14 Our case had no involuntary facial spasms by history or on exam, but MRI did identify a possible associated vascular compression of the facial nerve by the left anterior inferior cerebellar artery. Despite the patient not having hemifacial spasm, we cannot exclude the possibility that vascular compression of his right facial nerve might also be making the facial nucleus hyperexcitable,9 and contributing to the synkinesia and its delayed presentation in this case. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique; (4) Case: A. Identification, B. Literature Review. D.E.H.: 3A, 3B, 4B A.E.B.: 3B, 4A As this is a simple case report, a review and approval from our ethics committee was deemed not to be required. Verbal consent was obtained from the patient at the time of the initial consultation visit, for the purpose of videotaping for educational purposes. Written patient consent, for the purpose of publishing the video, was obtained after the decision to submit his case for publication. The patient had the opportunity to review the written case report before providing consent. We confirm we have read the Journal's position on issues involved in ethical publication and affirm this work is consistent with those guidelines. The authors report no sources of funding and no conflicts of interest. The authors declare that there are no disclosures to report. Video 1. The video, initially, demonstrates the patient's voluntary long-standing ability to wiggle both ears. The effect of voluntary left and right gaze is then demonstrated. There is a synkinetic right ear elevation, posterior displacement, and retraction with left lateral gaze, but no ear movement on gaze to the right. Video 2. This video demonstrates that synkinetic movements were not seen with up, down, or right saccades, tight eye closure, convergence, blinking, or head turning to the right. Forceful smiling triggered bilateral, but asymmetric (more on the right), ear movement. Chewing, swallowing, left saccades, and head turning to the left did cause right, but not left, synkinetic ear movements. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID). Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data. Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed. Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

Objective: To assess effects of caffeine on Parkinson disease (PD). Methods: In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life. Results: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement inmotor parkinsonism(the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1 +/- 4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo). Conclusion: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [18F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance.

BACKGROUND:In our clinical experience, people with Parkinson's disease (PwP) and their caregivers have difficulty understanding the complexities of the disease, which has a multitude of symptoms and involved therapies. We undertook a needs assessment to understand the need for, and to guide the development of, an educational tool. METHODS:We invited PwP, caregivers and health care providers (HCP) from across Canada to participate in an online survey to determine the need and desired content for such a tool. RESULTS:Respondents included 450 PwP, 335 caregivers, and 96 HCP from across Canada. 86.5% of HCP reported that it was "very important" for patients to understand issues in PD and 84.4% would use a visual aid to explain these issues. Results showed that 81.9-95.7% of caregivers and PwP were not "very satisfied" with the explanations of all domains in PD. Non-motor symptoms and cognitive issues were highly ranked by all groups as difficult to understand or explain. Older PwP (those with PD for less than 5 years and those who reported that their HCP spent less than 15 minutes counselling in each clinic visit) were less likely to fully understand and be satisfied with the explanations of most issues in PD. INTERPRETATION:There is a need for better patient education when discussing PD issues in the clinical setting. Older PwP that have been recently diagnosed have the greatest educational needs. Potential users indicate that a visual aid would help and non-motor symptoms, particularly cognitive issues, need to be a focus of such a tool.

IMPORTANCEIdentifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.OBJECTIVETo identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS).DESIGN, SETTING, AND PARTICIPANTSA prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013.EXPOSUREHuntington disease mutation status in individuals with CAG expansion vs without CAG expansion.MAIN OUTCOMES AND MEASURESUnified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years.RESULTSAmong the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P < .001 for all); behavioral domain scores did not diverge significantly between groups.CONCLUSIONS AND RELEVANCEUsing these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype.

Purpose: To investigate factors associated with healthcare utilization and prescription drug use for Parkinson's disease (PD) patients and matched controls.Methods: A retrospective matched-group design was adopted using administrative data from Manitoba, Canada. PD cases (N = 1469) were identified from diagnoses in hospital records and physician billing claims and matched to controls (N = 2938) on age, sex, and region of residence. Sixteen measures of healthcare utilization were examined over a six-year period using generalized linear models.Results: PD cases had greater healthcare utilization than controls for almost all investigated services, with the exception of visits to non-neurological specialists and hospital use for non-mental disorder diagnoses. For controls, utilization of all forms of healthcare increased with age; for PD cases the relationship was weak, except for specialist visits, where an inverse relationship was observed. A rural region of residence was associated with a lower rate of seeing a specialist or any medical doctor, with a higher rate of hospitalization than for urban cases or controls. Comorbidity was strongly associated with healthcare use for both groups. Over the six-year study period significant differences in the trend were observed for mental disorder hospitalizations, hospital days, and physician visits.Conclusions: Factors associated with healthcare utilization in PD patients differ from those without PD. This information may help to identify and optimize healthcare services and associated costs for PD patients. (C) 2012 Elsevier Ltd. All rights reserved.

Parkinson's disease, as well as many other parkinsonisms, including most toxic, neurodegenerative and familial types are typically asymmetric. No explanation for this phenomenon exists. A summary of the frequency of asymmetry in a spectrum of parkinsonian disorders is provided. Evidence against asymmetry being the result of normal asymmetries of the substantia nigrais reviewed. Asymmetry either results from a greater susceptibility on one side or a spreading pathology entering or starting on one side of the CNS. With the increasing evidence for spreading pathologies (toxins, viruses, α-synuclein), knowledge of neuroanatomical connections, and literature implicating spreading pathogens from the enteric and olfactory nerves, potential explanations can be theorized and explored, including the possibility of a pathogen preferentially entering or originating in the olfactory bulb on one side, with subsequent involvement of the other side.

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Movement DisordersVolume 25, Issue 9 p. 1305-1306 Letter to the Editor Related to New Topics Paroxysmal kinesigenic dyskinesia sans dyskinesia or paroxysmal kinesigenic dysesthesia?† Douglas E. Hobson BSc, FRCP(C), Corresponding Author Douglas E. Hobson BSc, FRCP(C) dhobson@cc.umanitoba.ca Movement Disorder Program, Deer Lodge Centre, University of Manitoba, Winnipeg, CanadaMovement Disorder Program, Deer Lodge Centre, University of Manitoba, Winnipeg, CanadaSearch for more papers by this author Douglas E. Hobson BSc, FRCP(C), Corresponding Author Douglas E. Hobson BSc, FRCP(C) dhobson@cc.umanitoba.ca Movement Disorder Program, Deer Lodge Centre, University of Manitoba, Winnipeg, CanadaMovement Disorder Program, Deer Lodge Centre, University of Manitoba, Winnipeg, CanadaSearch for more papers by this author First published: 19 July 2010 https://doi.org/10.1002/mds.23077 † Potential conflict of interest: Nothing to report. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume25, Issue915 July 2010Pages 1305-1306 RelatedInformation