Effects of speech rate modifications on phonatory acoustic outcomes in Parkinson's disease.

Speech rate reduction is a global speech therapy approach for speech deficits in Parkinson's disease (PD) that has the potential to result in changes across multiple speech subsystems. While the overall goal of rate reduction is usually improvements in speech intelligibility, not all people with PD benefit from this approach. Speech rate is often targeted as a means of improving articulatory precision, though less is known about rate-induced changes in other speech subsystems that could help or hinder communication. The purpose of this study was to quantify phonatory changes associated with speech rate modification across a broad range of speech rates from very slow to very fast in talkers with and without PD. Four speaker groups participated: younger and older healthy controls, and people with PD with and without deep brain stimulation of the subthalamic nucleus (STN-DBS). Talkers read aloud standardized sentences at 7 speech rates elicited using magnitude production: habitual, three slower rates, and three faster rates. Acoustic measures of speech intensity, cepstral peak prominence, and fundamental frequency were measured as a function of speech rate and group. Overall, slower rates of speech were associated with differential effects on phonation across the four groups. While all talkers spoke at a lower pitch in slow speech, younger talkers showed increases in speech intensity and cepstral peak prominence, while talkers with PD and STN-DBS showed the reverse pattern. Talkers with PD without STN-DBS and older healthy controls behaved in between these two extremes. At faster rates, all groups uniformly demonstrated increases in cepstral peak prominence. While speech rate reductions are intended to promote positive changes in articulation to compensate for speech deficits in dysarthria, the present results highlight that undesirable changes may be invoked across other subsystems, such as at the laryngeal level. In particular, talkers with STN-DBS, who often demonstrate speech deterioration following DBS surgery, demonstrated more phonatory detriments at slowed speech rates. Findings have implications for speech rate candidacy considerations and speech motor control processes in PD.

Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

BACKGROUND AND PURPOSE: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. METHODS: This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. RESULTS: Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. CONCLUSIONS: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Optimizing the selection of Parkinson's disease patients for neuromodulation using the levodopa challenge test.

BACKGROUND: In Parkinson's disease (PD), early stages are associated with a good long-duration response and as the disease advances, the short-duration response predominates. The transition between the long-duration and short-duration responses may be an important and measurable intermediate stage. A critical criterion in determining the candidature for neuromodulation is a beneficial response to an 'off-on' levodopa challenge test. This test is usually reserved for those that have already developed marked short-duration response and are candidates for deep brain stimulation (DBS) surgery. However, identifying those that are in transition may allow DBS to be offered earlier. OBJECTIVE: The objective of the study was to determine if the transition from a long-duration to a short-duration response can be assessed on a levodopa challenge test. METHODS: An 'off-on" levodopa challenge test was done in sixty-five PD patients divided into four groups based on the disease duration. RESULTS: OFF motor scores increased in all groups [Mean ± STD; 22.94 ± 8.52, 31.53 ± 9.87, 34.05 ± 9.50, and 33.92 ± 10.15 in groups 1-4, respectively] while a significant response to medication was maintained on 'off-on' testing. The mean levodopa equivalency dose in groups 1 and 2 was significantly less than in groups 3 and 4. This transition occurred between years 7 and 9 of disease duration. CONCLUSION: Performing a regular levodopa challenge test, when levodopa dose increases substantially, should be considered to determine the ideal time for DBS in patients with Parkinson's disease.

Iron Chelation in Movement Disorders: Logical or Ironical.

Iron is probably as old as the universe itself and is essential for sustaining biological processes. The remarkable property of iron complexes to facilitate electron transfer makes it a significant component of redox reactions that drive the essential steps in nucleic acid biosynthesis and cellular functions. This, however, also generates potentially harmful hydroxyl radicals causing cell damage. In the movement disorder world, iron accumulation is well known to occur in neurodegeneration with brain iron accumulation, while dysfunctional iron homeostasis has been linked with neurodegenerative diseases like Parkinson's disease and Huntington's disease to name a few. Targeting excess iron in these patients with chelation therapy has been attempted over the last few decades, though the results have not been that promising. In this review, we have discussed iron, its metabolism, and proposed mechanisms causing movement disorder abnormalities. We have reviewed the available literature on attempts to treat these movement disorders with chelation therapy. Finally, based on our understanding of the pathogenic role of iron, we have critically analyzed the limitations of chelation therapy in the current scenario and the various unmet needs that should be addressed for selecting the patient population amenable to this therapy.

Intraoperative Localization of STN During DBS Surgery Using a Data-Driven Model.

A new approach is presented for localizing the Subthalamic Nucleus (STN) during Deep Brain Stimulation (DBS) surgery based on microelectrode recordings (MERs). DBS is an accepted treatment for individuals living with Parkinson's Disease (PD). This surgery involves implantation of a permanent electrode inside the STN to deliver electrical current. Since the STN is a very small region inside the brain, accurate placement of an electrode is a challenging task for the surgical team. Prior to placement of the permanent electrode, microelectrode recordings of brain activity are used intraoperatively to localize the STN. The placement of the electrode and the success of the therapy depend on this location. In this paper, an objective approach is implemented to help the surgical team in localizing the STN. This is achieved by processing the MER signals and extracting features during the surgery to be used in a Machine Learning (ML) algorithm for defining the neurophysiological borders of the STN. For this purpose, a new classification approach is proposed with the goal of detecting both the dorsal and the ventral borders of the STN during the surgical procedure. Results collected from 100 PD patients in this study, show that by calculating and extracting wavelet transformation features from MER signals and using a data-driven computational deep neural network model, it is possible to detect the borders of the STN with an accuracy of 92%. The proposed method can be implemented in real-time during the surgery to model the neurophysiological nonlinearity along the path of the electrode trajectory during insertion.

Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients.

BACKGROUND: Benefits of dopaminergic therapy and deep brain stimulation are limited and unpredictable for axial symptoms in Parkinson's disease. Dorsal spinal cord stimulation may be a new therapeutic approach. The objective of this study was to investigate the therapeutic effect of spinal cord stimulation on gait including freezing of gait in advanced PD patients. METHODS: Five male PD participants with significant gait disturbances and freezing of gait underwent midthoracic spinal cord stimulation. Spinal cord stimulation combinations (200-500 µs/30-130 Hz) at suprathreshold intensity were tested over a 1- to 4-month period, and the effects of spinal cord stimulation were studied 6 months after spinal cord stimulation surgery. Protokinetics Walkway measured gait parameters. Z scores per gait variable established each participant's best spinal cord stimulation setting. Timed sit-to-stand and automated freezing-of-gait detection using foot pressures were analyzed. Freezing of Gait Questionnaire (FOG-Q), UPDRS motor items, and activities-specific balance confidence scale were completed at each study visit. RESULTS: Spinal cord stimulation setting combinations of 300-400 µs/30-130 Hz provided gait improvements. Although on-medication/on-stimulation at 6 months, mean step length, stride velocity, and sit-to-stand improved by 38.8%, 42.3%, and 50.3%, respectively, mean UPDRS, Freezing of Gait Questionnaire, and activities-specific balance confidence scale scores improved by 33.5%, 26.8%, and 71.4%, respectively. The mean number of freezing-of-gait episodes reduced significantly from 16 presurgery to 0 at 6 months while patients were on levodopa and off stimulation. CONCLUSIONS: By using objective measures to detect dynamic gait characteristics, the therapeutic potential of spinal cord stimulation was optimized to each participant's characteristics. This pilot study demonstrated the safety and significant therapeutic outcome of spinal cord stimulation in advanced PD patients, and thus a larger and longer clinical study will be conducted to replicate these results. © 2018 International Parkinson and Movement Disorder Society.

Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease.

Purpose: The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility. Method: Participants were tested under permutations of low, mid, and high STN-DBS frequency, voltage, and pulse width settings. At each session, participants recited a sentence. Acoustic characteristics of vowel production were extracted, and naive listeners provided estimates of speech intelligibility. Results: Overall, lower-frequency STN-DBS stimulation (60 Hz) was found to lead to improvements in intelligibility and acoustic vowel expansion. An interaction between speaker sex and STN-DBS stimulation was found for vowel measures. The combination of low frequency, mid to high voltage, and low to mid pulse width led to optimal speech outcomes; however, these settings did not demonstrate significant speech outcome differences compared with the standard clinical STN-DBS settings, likely due to substantial individual variability. Conclusions: Although lower-frequency STN-DBS stimulation was found to yield consistent improvements in speech outcomes, it was not found to necessarily lead to the best speech outcomes for all participants. Nevertheless, frequency may serve as a starting point to explore settings that will optimize an individual's speech outcomes following STN-DBS surgery. Supplemental Material: https://doi.org/10.23641/asha.5899228.

Using Wearable Technology to Generate Objective Parkinson's Disease Dyskinesia Severity Score: Possibilities for Home Monitoring.

A variety of clinical scales are available to assess dyskinesia severity in Parkinson's disease patients; however, such assessments are subjective, do not provide long term monitoring, and their use is subject to inter- and intra-rater variability. In this paper, an objective dyskinesia score was developed using an IMU -based motion capture system. Deep brain stimulation (DBS) surgery is currently the only acute intervention that results in the rapidly progressive reduction of dyskinesia's severity; hence, this form of therapy was selected as a model to validate the proposed method. Thirteen Parkinson's disease participants undergoing DBS surgery and 12 age-matched healthy control participants were assessed using the motion capture system. Concurrent Unified Dyskinesia Rating Scale (UDysRS) ratings were also performed. Parkinson's disease participants were assessed pre-operatively and for five visits post-operatively while seated at rest, during arms outstretched and while performing an action task. The kinematic data were used to develop an objective measure defined as the dyskinesia severity score. Generally, a strong correlation was observed between the UDysRS ratings and the full-body dyskinesia severity scores. The results suggest that it is feasible and clinically meaningful to utilize an objective full-body dyskinesia score for the assessment of dyskinesia. The portable motion capture system along with the developed software can be used remotely to monitor the full-body severity of dyskinesia, necessary for therapeutic optimization, especially in the patients home environment.

Palliative Care Discussions in Multiple System Atrophy: A Retrospective Review.

OBJECTIVE: Multiple system atrophy (MSA) is an incurable neurodegenerative illness in which progressive symptoms, including stridor and acute laryngeal obstruction, occur. Advanced care planning and palliative care discussions in people living with MSA are not well defined. The aim of the present study is to evaluate advanced care planning and current practices in palliative care in MSA to identify opportunities for improving quality of care. METHODS: The study is a retrospective chart review assessing the focus and timing of palliative care discussions in people living with MSA. Some 22 charts were reviewed. RESULTS: A total of 22 patients were included. The most common symptoms were parkinsonism, orthostatic hypotension, GI/GU dysfunction, ataxia and gait impairment. Six patients had stridor. Of the palliative care discussions that took place, the most common topics were diagnosis, symptoms or symptom management, and prognosis. In the majority of patients who died and who had a do-not-attempt-resuscitation order, discussions surrounding resuscitation and goals of care took place only hours before death. CONCLUSIONS: There is no standard approach to advanced care planning and palliative care discussions in people living with MSA. We propose a framework to guide advanced care planning and palliative care discussions in MSA.

Advances in Neurotrophic Factor and Cell-Based Therapies for Parkinson's Disease: A Mini-Review.

Parkinson's disease (PD) affects an estimated 7-10 million people worldwide and remains without definitive or disease-modifying treatment. There have been many recent developments in cell-based therapy (CBT) to replace lost circuitry and provide chronic biological sources of therapeutic agents to the PD-affected brain. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources. Neurotrophic factors (NTFs) offer a potential class of cytoprotective pharmacotherapeutics that may complement dopamine (DA) replacement and CBT strategies in PD. Chronic NTF delivery may be an integral goal of CBT, with grafts consisting of autologous drug-producing (e.g., DA, NTF) cells that are capable of integration and function in the host brain. In this mini-review, we outline the past experience and recent advances in NTF technology and CBT as promising and integrated approaches for the treatment of PD.

Neurotrophic factor expression in expandable cell populations from brain samples in living patients with Parkinson's disease.

Cell-based therapies offer promise for patients with Parkinson's disease (PD); however, durable and effective transplantation substrates need to be defined. This study characterized the feasibility and growth properties of primary cultures established from small-volume brain biopsies taken during deep brain stimulation (DBS) surgery in patients with PD. The lineage and expression of neurotrophic factors with known beneficial actions in PD-affected brain circuitry were also evaluated. Nineteen patients with PD undergoing DBS surgery consented to brain biopsies prior to electrode implantation. Cultures from these samples exhibited exponential and plateau phases of growth and were readily expanded throughout multiple passages. There was robust expression of progenitor markers and the unexpected colocalization of neural and mesenchymal proteins. The oligodendrocyte transcription factor, Olig1, and the myelin-specific sphingolipid, galactocerebroside, were coexpressed with each of glial-derived neurotrophic factor, brain-derived neurotrophic factor, and cerebral dopamine neurotrophic factor. Fluorescence-activated cell sorting demonstrated homogeneous expression of both nestin and Olig1 throughout the expanded cultures. Cells remained viable after a year in cryostorage. These findings confirm the feasibility of small brain biopsies as an expandable source of autologous cell substrate in living patients and demonstrate the complex phenotype of these cells, with implications for therapeutic application in PD and other neurological diseases.

Computing by physical interaction in neurons.

The electrodynamics of action potentials represents the fundamental level where information is integrated and processed in neurons. The Hodgkin-Huxley model cannot explain the non-stereotyped spatial charge density dynamics that occur during action potential propagation. Revealed in experiments as spike directivity, the non-uniform charge density dynamics within neurons carry meaningful information and suggest that fragments of information regarding our memories are endogenously stored in structural patterns at a molecular level and are revealed only during spiking activity. The main conceptual idea is that under the influence of electric fields, efficient computation by interaction occurs between charge densities embedded within molecular structures and the transient developed flow of electrical charges. This process of computation underlying electrical interactions and molecular mechanisms at the subcellular level is dissimilar from spiking neuron models that are completely devoid of physical interactions. Computation by interaction describes a more powerful continuous model of computation than the one that consists of discrete steps as represented in Turing machines.

A palliative approach to neurological care: a literature review.

This review assesses the current opinion towards early palliative care in neurology and discusses the existing evidence base. A comprehensive literature search resulted in 714 publications with 53 being directly relevant to the scope of this review. The current literature reflects primarily expert opinion and describes a growing interest in the early introduction of palliative principles into neurological care. Early initiation of palliative interventions has the potential to improve quality of life, enhance symptom management and assist in advance care planning. Further data is required to determine whether this shift in philosophy has a positive impact on patient care.

Screening for Parkinson's disease with response time batteries: a pilot study.

BACKGROUND: Although significant response time deficits (both reaction time and movement time) have been identified in numerous studies of patients with Parkinson's disease (PD), few attempts have been made to evaluate the use of these measures in screening for PD. METHODS: Receiver operator characteristic curves were used to identify cutoff scores for a unit-weighted composite of two choice response tasks in a sample of 40 patients and 40 healthy participants. These scores were then cross-validated in an independent sample of 20 patients and 20 healthy participants. RESULTS: The unit-weighted movement time composite demonstrated high sensitivity (90%) and specificity (90%) in the identification of PD. Movement time was also significantly correlated (r = 0.59, p < 0.025) with the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). CONCLUSIONS: Measures of chronometric speed, assessed without the use of biomechanically complex movements, have a potential role in screening for PD. Furthermore, the significant correlation between movement time and UPDRS motor score suggests that movement time may be useful in the quantification of PD severity.