Jaw Rotation in Dysarthria Measured With a Single Electromagnetic Articulography Sensor

Purpose This study evaluated a novel method for characterizing jaw rotation using orientation data from a single electromagnetic articulography sensor. This method was optimized for clinical application, and a preliminary examination of clinical feasibility and value was undertaken. Method The computational adequacy of the single-sensor orientation method was evaluated through comparisons of jaw-rotation histories calculated from dual-sensor positional data for 16 typical talkers. The clinical feasibility and potential value of single-sensor jaw rotation were assessed through comparisons of 7 talkers with dysarthria and 19 typical talkers in connected speech. Results The single-sensor orientation method allowed faster and safer participant preparation, required lower data-acquisition costs, and generated less high-frequency artifact than the dual-sensor positional approach. All talkers with dysarthria, regardless of severity, demonstrated jaw-rotation histories with more numerous changes in movement direction and reduced smoothness compared with typical talkers. Conclusions Results suggest that the single-sensor orientation method for calculating jaw rotation during speech is clinically feasible. Given the preliminary nature of this study and the small participant pool, the clinical value of such measures remains an open question. Further work must address the potential confound of reduced speaking rate on movement smoothness

A glimpse into the pathology of Parkinson’s Disease - An Ayurvedic Perspective

Parkinson’s disease (PD) is a progressive neuro degenerative disease characterised by a large number of motor and non-motor features that can impact on function to a variable degree. Charaka mentioned Kampa as one among 80 types of Vataja Nanatmaja Vyadhi. Kampa may be a symptom of many diseases. Kampavata is first described as a disease in Basavarajeeyam with cardinal symptoms as Hastapadatala Kampa, Dehabharamana, Dukkha, Nidrabhanga, Matiksheena. Here an effort is made to understand the Nidana Panchakas of Kampavata under the light of Kaphaavarana to all five types of Vata, especially Prana, Udana and Vyana. There is Udanaavruta Vyana and Pranaavruta Samana type of Anyonyaavarana, Majjaavruta Vata, Snayuprapta Vata and Asthimajjagata Vata as pathological processes depending upon the clinical presentation of the patient. The differential diagnosis of PD is also considered here to differentiate it from group of disorders which falls under Parkinsonism

Effects of dance therapy on balance, gait and neuro-psychological performances in patients with Parkinson's disease and postural instability

Postural Instability (PI) is a core feature of Parkinson’s Disease (PD) and a major cause of falls and disabilities. Impairment of executive functions has been called as an aggravating factor on motor performances. Dance therapy has been shown effective for improving gait and has been suggested as an alternative rehabilitative method. To evaluate gait performance, spatial-temporal (S-T) gait parameters and cognitive performances in a cohort of patients with PD and PI modifications in balance after a cycle of dance therapy

PERIORAL BIOMECHANICS, KINEMATICS, AND ELECTROPHYSIOLOGY IN PARKINSON'S DISEASE

This investigation quantitatively characterized the orofacial biomechanics, labial kinematics, and associated electromyography (EMG) patterns in individuals with Parkinson's disease (PD) as a function of anti-PD medication state. Passive perioral stiffness, a clinical correlate of rigidity, was sampled using a face-referenced OroSTIFF system in 10 mildly diagnosed PD and 10 age/sex-matched control elderly. Labial movement amplitudes and velocities were evaluated using a 4-dimensional computerized motion capture system. Associated perioral EMG patterns were sampled to examine the characteristics of perioral muscles and compensatory muscular activation patterns during repetitive syllable productions. This study identified several trends that reflect various characteristics of perioral system differences between PD and control subjects: 1. The presence of high tonic EMG patterns after administration of dopaminergic treatment indicated an up-regulation of the central mechanism, which may serve to regulate orofacial postural control. 2. Multilevel regression modeling showed greater perioral stiffness in PD subjects, confirming the clinical correlate of rigidity in these patients. 3. Similar to the clinical symptoms in the upper and lower limb, a reduction of range of motion (hypokinesia) and velocity (bradykinesia) was evident in the PD orofacial system. Administration of dopaminergic treatment improved hypokinesia and bradykinesia. 4. A significant correlation was found between perioral stiffness and the range of labial movement, indicating these two symptoms may result in part from a common neural substrate. 5. As speech rate increased, PD speakers down-scaled movement amplitude and velocity compared to the control subjects, reflecting a compensatory mechanism to maintain target speech rates. 6. EMG from orbicularis oris inferior (OOIm) and depressor labii inferioris (DLIm) muscles revealed a limited range of muscle activation level in PD speakers, reflecting the underlying changes in motor unit firing behavior due to basal ganglia dysfunction. The results of this investigation provided a quantitative description of the perioral stiffness, labial kinematics, and EMG patterns in PD speakers. These findings indicate that perioral stiffness may provide clinicians a quantitative biomechanical correlate to medication response, movement aberrations, and EMG compensatory patterns in PD. The utilization of these objective assessments will be helpful in diagnosing, assessing, and monitoring the progression of PD to examine the efficacy of pharmacological, neurosurgical, and behavioral interventions

Effects of deep brain stimulation on speech in patients with Parkinson’s disease and dystonia

Disorders affecting the basal ganglia can have a severe effect on speech motor control. The effect can vary depending on the pathophysiology of the basal ganglia disease but in general terms it can be classified as hypokinetic or hyperkinetic dysarthria. Despite the role of basal ganglia on speech, there is a marked discrepancy between the effect of medical and surgical treatments on limb and speech motor control. This is compounded by the complex nature of speech and communication in general, and the lack of animal models of speech motor control. The emergence of deep brain stimulation of basal ganglia structures gives us the opportunity to record systematically the effects on speech and attempt some assumptions on the role of basal ganglia on speech motor control. The aim of the present work was to examine the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) and globus pallidus internus (GPi-DBS) for dystonia on speech motor control. A consecutive series of PD and dystonia patients who underwent DBS was evaluated. Patients were studied in a prospective longitudinal manner with both clinical assessment of their speech intelligibility and acoustical analysis of their speech. The role of pre-operative clinical factors and electrical parameters of stimulation, mainly electrode positioning and voltage amplitude was systematically examined. In addition, for selected patients, tongue movements were studied using electropalatography. Aerodynamic aspects of speech were also studied. The impact of speech therapy was assessed in a subgroup of patients. The clinical evaluation of speech intelligibility one and three years post STN-DBS in PD patients showed a deterioration of speech, partly related to medially placed electrodes and high amplitude of stimulation. Pre-operative predictive factors included low speech intelligibility before surgery and longer disease duration. Articulation rather than voice was most frequently affected with a distinct dysarthria type emerging, mainly hyperkinetic-dystonic, rather than hypokinetic. Traditionally effective therapy for PD dysarthria had little to no benefit following STN-DBS. Speech following GPi-DBS for dystonia did not significantly change after one year of stimulation. A subgroup of patients showed hypokinetic features, mainly reduced voice volume and fast rate of speech more typical of Parkinsonian speech. Speech changes in both STN-DBS and GPi-DBS were apparent after six months of stimulation. This progressive deterioration of speech and the critical role of the electrical parameters of stimulation suggest a long-term effect of electrical stimulation of basal ganglia on speech motor control

Magnetic resonance imaging techniques for diagnostics in Parkinson’s disease and atypical parkinsonism

Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by rigidity, hypokinesia, tremor and postural instability. PD is a clinical diagnosis based on neurological examination, patient history and treatment response. Similar symptoms can be caused by other movement disorders such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), making it difficult to clinically separate them in early stages. However, these diseases differ in underlying pathology, treatment and prognosis. PSP and MSA have more rapid deterioration and develop additional symptoms such as impaired eye movements or autonomic dysfunction. Magnetic resonance imaging (MRI) is commonly performed as part of the clinical work-up in patients presenting with parkinsonism. There are no overt changes on structural MRI in PD. In atypical parkinsonian syndromes there are typically no visible changes until later disease stages. Purpose: The aim of this thesis is to evaluate novel MRI techniques for diagnostics and for investigation of disease processes in Parkinson’s disease, PSP and MSA. Paper I: A retrospective cohort from Karolinska University Hospital (102 participants; 62 PD, 15 PSP, 11 MSA, 14 controls) was assessed using susceptibility mapping processed from susceptibility weighted imaging. We show that there is elevated susceptibility in the red nucleus and the globus pallidus in PSP compared to PD, MSA and controls. Higher susceptibility levels were also seen in MSA compared to PD in the putamen, and in PD compared to controls in the substantia nigra. Using the red nucleus susceptibility as a diagnostic biomarker, PSP could be separated from PD with an accuracy of 97% (based on the area under the receiver operating characteristic curve, AUC), from MSA with AUC 75% and from controls with AUC 98%. We concluded that susceptibility changes, particularly in the red nucleus in PSP, could be potential biomarkers for differential diagnostics in parkinsonism. Paper II: A prospective cohort from Lund, the BioFINDER study (199 participants; 134 PD, 11 PSP, 10 MSA, 44 controls), was investigated using the susceptibility mapping pipeline developed for Paper I. The finding from Paper I with elevated susceptibility in the red nucleus was validated for PSP compared to PD, MSA and controls. The elevated putaminal susceptibility was also confirmed in MSA compared to PD. The potential role of red nucleus susceptibility as a biomarker for separating PSP from PD and MSA was also similar to the results in Paper I, with AUC 98% for separating PSP from PD and AUC 96% for separating PSP from MSA. We concluded that we could confirm our previous findings from Paper I, with the red nucleus susceptibility being a potential biomarker for separating PSP from PD and MSA. Paper III: A retrospective cohort from Karolinska University Hospital (196 participants; 140 PD, 29 PSP, 27 MSA) was evaluated to employ automated volumetric brainstem segmentation using FreeSurfer. The volumetric approach was compared to manual planimetric measurements: midbrain-pons ratio, magnetic resonance parkinsonism index 1.0 and 2.0. Intra- and inter-scanner as well as intra- and inter-rater reliability were calculated. We found good repeatability in both automated volumetric and manual planimetric measurements. Normalized midbrain volume performed better than the planimetric measurements for separating PSP from PD. We concluded that, if further developed and incorporated in a radiology workflow, automated brainstem volumetry could increase availability of brainstem metrics and possibly save time for radiologists conducting manual measurements. Paper IV: Two cohorts, a retrospective from Karolinska University Hospital (184 participants; 129 PD, 28 PSP, 27 MSA) and a prospective from Lund (185 participants; 125 PD, 11 PSP, 8 MSA, 41 controls), were studied to investigate a new method of creating T1-/T2-weighted ratio images and its diagnostic capabilities in differentiating parkinsonian disorders. In the explorative retrospective cohort, differences in white matter normalized T1-/T2- weighted ratios were seen in the caudate nucleus, putamen, thalamus, subthalamic nucleus and red nucleus in PSP compared to PD; in the caudate nucleus and putamen in MSA compared to PD and in the subthalamic nucleus and the red nucleus in PSP compared to MSA. These differences were validated externally in the prospective cohort, where the changes could be confirmed in the subthalamic nucleus and the red nucleus in PSP compared to PD and MSA. We concluded that there are different patterns of white matter normalized T1-/T2-weighted ratio between the disorders and that this reflects differences in underlying pathophysiology. The T1-/T2-weighted ratio should be further investigated for better understanding of pathological processes in parkinsonian disorders and could possibly be utilized for diagnostic purposes if further developed

Therapeutic use of cerebellar transcranial theta burst magnetic stimulation in movement disorders. Mechanisms of action and biomarkers of efficacy

Movement disorders of different aetiology are characterized by an impairment in several interconnected areas of the motor system. Among the non-pharmacological options to improve motor symptoms, repetitive Transcranial Magnetic Stimulation (rTMS), represent a promising therapeutic tool due to its ability to induce long-term modulation of synaptic plasticity and its low incidence of side effects. Theta burst stimulation (TBS), a patterned protocol of rTMS, is able to induce long lasting excitatory (intermittent TBS) and inhibitory (continuous TBS) effects on cortical excitability and its very tolerable for patients due to its short duration. The high variability of response to TBS limits its use in clinical practice, thus research is focused on the characterization of predictors of response and biomarkers of efficacy. Among these, a common polymorphism of Brain Derived neurotrophic Factor (BDNF) gene, val66met, may influence the onset and progression of several neurodegenerative disorders and may alter the response to different TMS protocols, in particular TBS, but results are conflicting. Cerebellum is considered an interesting area of stimulation for rTMS protocols in movement disorders due to its ability to influence motor learning and control through its connections with all the areas of the motor system and its role in sensory-motor integration. Indeed, it is currently used as a target for neuromodulation in movement disorders involving different pathological mechanisms. The aim of the present study was to test the efficacy of inhibitory and excitatory cerebellar TBS in three movement disorders with different aetiology and to search possible biomarkers influencing its therapeutic effect. In the first project a single session of cerebellar continuous TBS (cTBS) was able to reduce levodopa-induced Dyskinesia in patients affected by Parkinson’s Disease (PD) and this effect was accompanied by a decrease in serum BDNF levels. Moreover, the presence of the Val66Met polymorphism of the BDNF gene was associated with a better response. In the second project 15 sessions of cerebellar intermittent TBS (iTBS) were able to improve motor symptoms in patients affected by Multiple system atrophy (MSA). No variations in serum BDNF levels after iTBS treatment were observed and apparently Val66Met polymorphism did not influence the clinical response. In the third project the excitability of primary motor cortex (M1) was increased by a single session of cerebellar iTBS in patients affected by Spino-Cerebellar ataxia 38 (SCA 38), an inherited disease characterized by mutation in the EVLOV-5 gene. iTBS was then applied for 10 sessions to the cerebellum of patients leading to an improvement of motor symptoms, especially postural stability. The Val66Met polymorphism did not influence the clinical response and the changes in motor cortex excitability. Overall, these data provide evidence for the use of cerebellar TBS in movement disorders; moreover, they suggest that BDNF Val66Met polymorphism may influence response to TBS but results vary depending on experimental model. Finally, they underline that measures of cortical excitability may provide information about the responsivity of the motor network to neuromodulation and may help to select an appropriate therapeutic protocol. Future studies will help to select other genetic, neurophysiological and imaging biomarkers leading to a better prediction and characterization of the clinical response to TBS

Optimising programming to reduce side effects of subthalamic nucleus deep brain stimulation in Parkinson’s Disease

Subthalamic nucleus deep brain stimulation (STN DBS) is a widely used treatment for Parkinson’s disease patients with motor complications refractory to medical management. However, a significant proportion of treated patients suffer from stimulation induced side effects. Conventional options to address these by modulation of stimulation parameters and programming configurations have been limited. In recent years, technological advances have resulted in the emergence of novel programming features, including the use of short pulse width (PW) and directional steering, that represent further avenues to explore in this regard. In this thesis, I will present data on the utility of these programming techniques in alleviating stimulation induced side effects, and explore mechanisms that may mediate any observed effects. The data presented here is derived from four studies. Study 1 quantified the therapeutic window using short PW stimulation at 30μs relative to conventional 60μs settings. Study 2 represents a randomised controlled trial on short PW in chronic STN DBS patients with dysarthria. Study 3 evaluated the utility of directional steering, short PW, and the combination of these features in reversing stimulation induced dysarthria, dyskinesia, and pyramidal side effects. The findings of these studies suggest that short PW significantly increases the therapeutic window in terms of amplitude and charge, and that while it may not benefit chronic dysarthric patients collectively, directional steering and short PW can each significantly improve reversible stimulation induced side effects early in the course of STN DBS therapy. These novel techniques represent effective additional tools to conventional methods for optimising stimulation. In study 4, imaging and visualisation software are used to model and explore shifts in volume of tissue activated based on clinical data from study 3, and quantitatively compare charge per pulse, in order to explore potential mechanisms underlying the changes seen with these techniques

Colonic Biopsies to Assess the Neuropathology of Parkinson's Disease and Its Relationship with Symptoms

The presence of Lewy bodies and Lewy neurites (LN) has been demonstrated in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms.A total of 10 control and 29 PD patients divided into 3 groups according to disease duration were included. PD and GI symptoms were assessed using the Unified Parkinson's Disease Rating Scale part III and the Rome III questionnaire, respectively. Four biopsies were taken from the ascending and descending colon during the course of a total colonoscopy. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein, neurofilaments NF 220 kDa (NF) and tyrosine hydroxylase (TH). The density of LN, labeled by anti-phosphorylated alpha-synuclein antibodies, was evaluated using a quantitative rating score. Lewy pathology was apparent in the colonic biopsies from 21 patients and in none of the controls. A decreased number of NF-immunoreactive neurons per ganglion was observed in the SMP of PD patients compared to controls. The amount of LN in the ENS was inversely correlated with neuronal count and positively correlated with levodopa-unresponsive features and constipation.Analysis of the ENS by routine colonoscopy biopsies is a useful tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms

Neurosurgical strategies for Gilles de la Tourette’s syndrome

Tourette’s syndrome (TS) is a neurological disorder characterized by motor and vocal tics that typically begin in childhood and often are accompanied by psychiatric comorbidities. Symptoms of TS may be socially disabling and cause secondary medical complications. Pharmacological therapies remain the mainstay of symptom management. For the subset of patients in whom TS symptoms are medically recalcitrant and do not dissipate by adulthood, neurosurgery may offer an alternative treatment strategy. Greater understanding of the neuroanatomic and pathophysiologic basis of TS has facilitated the development of surgical procedures that aim to ameliorate TS symptoms by lesions or deep brain stimulation of cerebral structures. Herein, the rationale for the surgical management of TS is discussed and neurosurgical experiences since the 1960s are reviewed. The necessity for neurosurgical strategies to be performed with appropriate ethical considerations is highlighted