Treatment Of Movement Disorders Research Articles

Evolution of Movement Disorders in Patients With CLN2-Batten Disease Treated With Enzyme Replacement Therapy.

Neuronal ceroid lipofuscinosis type 2 (CLN2-disease) is an inherited childhood-onset neurodegenerative condition, with classical early features of speech delay, epilepsy, myoclonus, ataxia, and motor regression. This study aimed to better characterize the spectrum of movement disorders in CLN2-disease in a cohort of children receiving enzyme replacement therapy (ERT). A cohort of 18 children attending a single center for treatment with cerliponase alfa ERT was systematically assessed using a standardized structured history and a double-scored, video-recorded examination using the Unified Batten Disease Rating Scale (UBDRS) and Abnormal Involuntary Movement Scale. Noncanonical movement disorders are common: while ataxia (89%) and myoclonus (83%) were near-universal, spasticity and dystonia were experienced by over half (61% each), with children having a median of 4 distinct movement disorder phenotypes. This progression was stereotyped with initial ataxia/myoclonus, then hyperkinesia/spasticity, and later hypokinesia. ERT slows progression of movement disorders, as measured by the UBDRS physical subscale, with 1.45 points-per-month progression before diagnosis and 0.44 points-per-month while on treatment (p = 0.019). Movement disorders are a core feature of CLN2-disease and follow a typical pattern of progression which is slowed by ERT. Identifying and treating movement disorders should become standard, especially given increased patient survival.

Establishing and developing a magnetic resonance-guided focused ultrasound program in a resource-limited setting: the Philippine experience.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive lesioning technique used to treat movement disorders such as essential tremor (ET), Parkinson's disease (PD), and X-linked dystonia-parkinsonism (XDP). We would like to report our experience in establishing and developing our MRgFUS program and preliminary results. Adult patients with tremor-dominant PD (TDPD), ET, and XDP were considered for initial screening (neurologic evaluation, skull density ratio [SDR] determination). Eligible patients underwent secondary screening (neurosurgical and neuropsychological evaluation, psychiatric and medical clearance). During the procedure, a neuro-anesthesiologist and neurologist were also present to monitor the patient and perform neurologic evaluation, respectively. Clinical follow-up was scheduled at 2 weeks post-treatment, then at every 3 months. A total of 30 patients underwent MRgFUS treatment: 22 TDPD, 6 XDP, and 2 ET. The mean age was 55.7 years, and majority were male (86.7%). Mean disease duration was 8.6 years. Mean SDR was 0.46. The targets for TDPD and ET were the contralateral ventral intermediate nucleus of the thalamus; for XDP, it was the pallidothalamic tract. The mean maximum temperature was 59.8oC; number of sonocations, 7.3; and treatment time, 64.6min. Majority of patients improved after the procedure. Transient intraprocedural adverse events (headache, dizziness) were reported in 20% of patients while post-procedural events (mild weakness, numbness) were seen in 16.7%. Only 26.7% of patients had follow-up data. Despite the unique challenges encountered, MRgFUS treatment is feasible in resource-limited settings. Additional steps would have to be made to develop and improve the program.

Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications.

Botulinum neurotoxins (BoNTs) have been used for almost half a century in the treatment of excessive muscle contractility. BoNTs are routinely used to treat movement disorders such as cervical dystonia, spastic conditions, blepharospasm, and hyperhidrosis, as well as for cosmetic purposes. In addition to the conventional indications, the use of BoNTs to reduce pain has gained increased recognition, giving rise to an increasing number of indications in disorders associated with chronic pain. Furthermore, BoNT-derived formulations are benefiting a much wider range of patients suffering from overactive bladder, erectile dysfunction, arthropathy, neuropathic pain, and cancer. BoNTs are categorised into seven toxinotypes, two of which are in clinical use, and each toxinotype is divided into multiple subtypes. With the development of bioinformatic tools, new BoNT-like toxins have been identified in non-Clostridial organisms. In addition to the expanding indications of existing formulations, the rich variety of toxinotypes or subtypes in the wild-type BoNTs associated with new BoNT-like toxins expand the BoNT superfamily, forming the basis on which to develop new BoNT-based therapeutics as well as research tools. An overview of the diversity of the BoNT family along with their conventional therapeutic uses is presented in this review followed by the engineering and formulation opportunities opening avenues in therapy.

AI-powered Neuroprosthetics for brain-computer interfaces (BCIs)

Imagine a world where individuals with lost or impaired sensory or motor function can regain independence and control through technology. This is the promise of neuroprosthetics, a rapidly evolving field that bridges the gap between the nervous system and external devices. Neuroprosthetics encompass a range of implanted or external devices designed to: Substitute for a malfunctioning part of the nervous system. Assist in the recovery or enhancement of lost or impaired function. Augment existing capabilities, creating new possibilities. These devices interact with the nervous system using various methods, including: Electrical stimulation: Directly stimulating nerves or brain tissue to evoke desired responses. Recording brain activity: Capturing electrical signals generated by the brain for further processing and interpretation. Common applications of neuroprosthetics include: Cochlear implants: Restoring hearing in individuals with severe hearing loss. Deep brain stimulation (DBS): Treating movement disorders like Parkinson's disease and essential tremor. Bionic limbs: Providing control of prosthetic arms and legs for individuals with limb loss. Brain-computer interfaces (BCIs): Enabling communication and control of external devices using brain signals alone. Neuroprosthetics offer a glimpse into the future of medicine and technology. With ongoing advancements, these devices have the potential to revolutionize how we treat neurological conditions, restore lost abilities, and even enhance human potential. However, significant challenges remain, including ensuring long-term safety, improving accuracy and reliability, and addressing ethical considerations. As research continues, neuroprosthetics holds immense potential to improve the lives of millions and redefine what it means to be human. The integration of artificial intelligence (AI) with neuroprosthetics has marked a significant milestone in the development of brain-computer interfaces (BCIs). This emerging synergy aims to enhance the quality of life for individuals with disabilities by restoring lost sensory, motor, and cognitive functions. This review article explores the advancements in AI-powered neuroprosthetics for BCIs, focusing on their design, functionality, and the ethical considerations that accompany their integration into medical practice.

Jerzy Majkowski – a Polish neurologist and neurophysiologist

IntroductionJerzy Majkowski was a Polish neurologist who made significant contributions to the field of neuroscience. Majkowski was a renowned physician and researcher who specialized in studying and treating movement disorders such as Parkinson’s disease and dystonia. Throughout his career, he was known for his innovative approaches to diagnosing and treating these complex conditions, and he was widely respected by his peers for his deep understanding of the brain and its functions.AimThe purpose of our work is to introduce the reader to the person of Jerzy Majkowski.Material and methodsThe work is based on the available literature. The search process resulted in the detection of relevant articles using valid keywords on electronic databases, including Embase, PubMed, Scopus, Web of Science, and Cochrane Library. Subsequently, 10 were identified as eligible for our review.Results and discussionJerzy ‘Czarny’ Majkowski, a Polish neurologist and neurophysiologist. During World War II, he joined the Polish Scouting Association, where he participated in the underground activities of the organization under the pseudonym Czarny. After the war, he studied medicine at Warsaw University and graduated in 1952. Majkowski was interested in epilepsy, electroencephalography, and neurophysiology and put forward several hypotheses based on his research. He was the author of about 500 scientific publications and edited 14 books. He was also the editor of several journals, including Epileptologia and the Journal of Epileptology.ConclusionsMajkowski’s work has helped to advance our understanding of neurological disorders, and his legacy continues to inspire future generations of scientists and physicians.

Low-Intensity Pulsed Ultrasound Neuromodulation of a Rodent's Spinal Cord Suppresses Motor Evoked Potentials.

Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals. Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes. Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p < 0.001) and 10-min (p = 0.004) cohorts with a corresponding gradual recovery to baseline. Forelimb MEP amplitude did not demonstrate any statistically significant changes during sonication in either the 5- (p = 0.46) or 10-min (p = 0.80) trials. LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication. LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Movement Disorders Associated with Cerebral Artery Stenosis: A Nationwide Study (P13-11.003)

<h3>Objective:</h3> We aimed to investigate the clinical characteristics of movement disorders (MD) associated with cerebral artery stenosis (CAS). <h3>Background:</h3> Studies of secondary MD caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from CAS without clinical manifestations of stroke. <h3>Design/Methods:</h3> A nationwide multi-center retrospective analysis was performed based on the data from patients with CAS-associated MDs from MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the &gt; 50% luminal stenosis of the major cerebral arteries. The association between the MD and CAS was determined by MD specialists using predefined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and outcomes of MD. Statistical analyses were performed to identify factors associated with the outcomes of MD. <h3>Results:</h3> The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease. Relative to patients with atherosclerosis, those with moyamoya disease developed MD at a younger age (p &lt; 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute onset of MD had a better outcome than those with subacute-to-chronic onset of MD (p = 0.008). <h3>Conclusions:</h3> This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition. <b>Disclosure:</b> Dr. Chung has nothing to disclose. Dr. Choi has nothing to disclose. Prof. Oh has nothing to disclose. Ho-Sung Ryu has nothing to disclose. Sooyeoun You has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Park has nothing to disclose.

Efficacy of Electroconvulsive Therapy for the Treatment of Movement Disorders: A Literature Review.

Electroconvulsive therapy (ECT) is a safe and effective treatment modality for various psychiatric disorders.However, evidence suggests a putative role of ECT in treating movement disorders that are refractory to less invasive modalities. ECT is primarily used in treatment-resistant psychiatric disorders. However, growing evidence exists for its use in movement disorders with and without psychiatric comorbidity. The primary objective of this systematic review was to examine the efficacy of ECT as a primary treatment modality for movement disorders. Relevant, peer-reviewed publications were retrieved from PubMed, SCOPUS, CINAHL, and PsycINFO. Keywords related to ECT and movement disorders were used as search phrases to identify relevant articles. A total of 90 articles that met the inclusion criteria were included in this review. Core findings were subsequently appraised on the role of ECT in treating movement disorders. Inclusion and exclusion criteria were developed to guide the search and selection process. Sources that met the inclusion criteria were those published between 2001 and January 2023. Additionally, peer-reviewed journals published in the English language covering the role of ECT in movement disorders were deemed appropriate for inclusion. Sources published before 2001, written in a non-English language, and not from peer-reviewed journals were excluded from this systematic review. The exclusion criteria also entailed eliminating duplicates from the review list. Most reviewed sources revealed that ECT improved outcomes in symptoms associated with various movement symptoms. However, ECT does not have a long-lasting impact on neuroacanthocytosis symptoms. Additionally, ECT is negatively associated with aggression and agitation, two of the most critical movement symptoms of Alzheimer's disease. Evidence affirms the efficacy of ECT in providing symptomatic relief for movement disorders aside from psychiatric comorbidities. This positive association highlights the need for randomized controlled studies to identify movement disorder sub-populations that may respond to ECT.

Automatic extraction of upper-limb kinematic activity using deep learning-based markerless tracking during deep brain stimulation implantation for Parkinson's disease: A proof of concept study.

Optimal placement of deep brain stimulation (DBS) therapy for treating movement disorders routinely relies on intraoperative motor testing for target determination. However, in current practice, motor testing relies on subjective interpretation and correlation of motor and neural information. Recent advances in computer vision could improve assessment accuracy. We describe our application of deep learning-based computer vision to conduct markerless tracking for measuring motor behaviors of patients undergoing DBS surgery for the treatment of Parkinson’s disease. Video recordings were acquired during intraoperative kinematic testing (N = 5 patients), as part of standard of care for accurate implantation of the DBS electrode. Kinematic data were extracted from videos post-hoc using the Python-based computer vision suite DeepLabCut. Both manual and automated (80.00% accuracy) approaches were used to extract kinematic episodes from threshold derived kinematic fluctuations. Active motor epochs were compressed by modeling upper limb deflections with a parabolic fit. A semi-supervised classification model, support vector machine (SVM), trained on the parameters defined by the parabolic fit reliably predicted movement type. Across all cases, tracking was well calibrated (i.e., reprojection pixel errors 0.016–0.041; accuracies >95%). SVM predicted classification demonstrated high accuracy (85.70%) including for two common upper limb movements, arm chain pulls (92.30%) and hand clenches (76.20%), with accuracy validated using a leave-one-out process for each patient. These results demonstrate successful capture and categorization of motor behaviors critical for assessing the optimal brain target for DBS surgery. Conventional motor testing procedures have proven informative and contributory to targeting but have largely remained subjective and inaccessible to non-Western and rural DBS centers with limited resources. This approach could automate the process and improve accuracy for neuro-motor mapping, to improve surgical targeting, optimize DBS therapy, provide accessible avenues for neuro-motor mapping and DBS implantation, and advance our understanding of the function of different brain areas.

Effect of music-based movement therapy on the freezing of gait in patients with Parkinson's disease: A randomized controlled trial.

Progression of freezing of gait (FOG), a common pathological gait in Parkinson's disease (PD), has been shown to be an important risk factor for falls, loss of independent living ability, and reduced quality of life. However, previous evidence indicated poor efficacy of medicine and surgery in treating FOG in patients with PD. Music-based movement therapy (MMT), which entails listening to music while exercising, has been proposed as a treatment to improve patients' motor function, emotions, and physiological activity. In recent years, MMT has been widely used to treat movement disorders in neurological diseases with promising results. Results from our earlier pilot study revealed that MMT could relieve FOG and improve the quality of life for patients with PD. To explore the effect of MMT on FOG in patients with PD. This was a prospective, evaluator-blinded, randomized controlled study. A total of 81 participants were randomly divided into music-based movement therapy group (MMT, n = 27), exercise therapy group (ET, n = 27), and control group (n = 27). Participants in the MMT group were treated with MMT five times (1 h at a time) every week for 4 weeks. Subjects in the ET group were intervened in the same way as the MMT group, but without music. Routine rehabilitation treatment was performed on participants in all groups. The primary outcome was the change of FOG in patients with PD. Secondary evaluation indicators included FOG-Questionnaire (FOG-Q) and the comprehensive motor function. After 4 weeks of intervention, the double support time, the cadence, the max flexion of knee in stance, the max hip extension, the flexion moment of knee in stance, the comprehensive motor function (UPDRS Part III gait-related items total score, arising from chair, freezing of gait, postural stability, posture, MDS-UPDRS Part II gait-related items total score, getting out of bed/a car/deep chair, walking and balance, freezing), and the FOG-Q in the MMT group were lower than that in the control group and ET group (p < 0.05). The gait velocity, the max ankle dorsiflexion in stance, ankle range of motion (ROM) during push-off, ankle ROM over gait cycle, the knee ROM over gait cycle, and the max extensor moment in stance (ankle, knee) in the MMT group were higher than that in the control group and ET group (p < 0.05). However, no significant difference was reported between the control group and ET group (p > 0.05). The stride length and hip ROM over gait cycle in the MMT group were higher than that in the control group (p < 0.05), and the max knee extension in stance in the MMT group was lower than that in the control group (p < 0.05). Nevertheless, there was no significant difference between the ET group and MMT group (p > 0.05) or control group (p > 0.05). MMT improved gait disorders in PD patients with FOG, thereby improving their comprehensive motor function.

Probing the structure and function of locus coeruleus projections to CNS motor centers.

The brainstem nucleus locus coeruleus (LC) sends projections to the forebrain, brainstem, cerebellum and spinal cord and is a source of the neurotransmitter norepinephrine (NE) in these areas. For more than 50 years, LC was considered to be homogeneous in structure and function such that NE would be released uniformly and act simultaneously on the cells and circuits that receive LC projections. However, recent studies have provided evidence that LC is modular in design, with segregated output channels and the potential for differential release and action of NE in its projection fields. These new findings have prompted a radical shift in our thinking about LC operations and demand revision of theoretical constructs regarding impact of the LC-NE system on behavioral outcomes in health and disease. Within this context, a major gap in our knowledge is the relationship between the LC-NE system and CNS motor control centers. While we know much about the organization of the LC-NE system with respect to sensory and cognitive circuitries and the impact of LC output on sensory guided behaviors and executive function, much less is known about the role of the LC-NE pathway in motor network operations and movement control. As a starting point for closing this gap in understanding, we propose using an intersectional recombinase-based viral-genetic strategy TrAC (Tracing Axon Collaterals) as well as established ex vivo electrophysiological assays to characterize efferent connectivity and physiological attributes of mouse LC-motor network projection neurons. The novel hypothesis to be tested is that LC cells with projections to CNS motor centers are scattered throughout the rostral-caudal extent of the nucleus but collectively display a common set of electrophysiological properties. Additionally, we expect to find these LC projection neurons maintain an organized network of axon collaterals capable of supporting selective, synchronous release of NE in motor circuitries for the purpose of coordinately regulating operations across networks that are responsible for balance and movement dynamics. Investigation of this hypothesis will advance our knowledge of the role of the LC-NE system in motor control and provide a basis for treating movement disorders resulting from disease, injury, or normal aging.

Subthalamic deep brain stimulation for refractory Gilles de la Tourette’s syndrome: clinical outcome and functional connectivity

BackgroundDeep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette’s syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, management of GTS and treatment mechanism of STN-DBS in GTS remain to be elucidated.MethodsTen patients undergoing STN-DBS were included. Tics severity was evaluated using the Yale Global Tic Severity Scale. The severities of comorbid psychiatric symptoms of obsessive–compulsive behavior (OCB), attention-deficit/hyperactivity disorder, anxiety, and depression; social and occupational functioning; and quality of life were assessed. Volumes of tissue activated were used as seed points for functional connectivity analysis performed using a control dataset.ResultsThe overall tics severity significantly reduced, with 62.9% ± 26.2% and 58.8% ± 27.2% improvements at the 6- and 12-months follow-up, respectively. All three patients with comorbid OCB showed improvement in their OCB symptoms at both the follow-ups. STN-DBS treatment was reasonably well tolerated by the patients with GTS. The most commonly reported side effect was light dysarthria. The stimulation effect of STN-DBS might regulate these symptoms through functional connectivity with the thalamus, pallidum, substantia nigra pars reticulata, putamen, insula, and anterior cingulate cortices.ConclusionsSTN-DBS was associated with symptomatic improvement in severe and refractory GTS without significant adverse events. The STN is a promising DBS target by stimulating both sensorimotor and limbic subregions, and specific brain area doses affect treatment outcomes.

Antiseizure Drugs and Movement Disorders.

The relationship between antiseizure drugs and movement disorders is complex and not adequately reviewed so far. Antiseizure drugs as a treatment for tremor and other entities such as myoclonus and restless leg syndrome is the most common scenario, although the scientific evidence supporting their use is variable. However, antiseizure drugs also represent a potential cause of iatrogenic movement disorders, with parkinsonism and tremor the most common disorders. Many other antiseizure drug-induced movement disorders are possible and not always correctly identified. This review was conducted by searching for all the possible combinations between 15 movement disorders (excluding ataxia) and 24 antiseizure drugs. The main objective was to describe the movement disorders treated and worsened or induced by antiseizure drugs. We also summarized the proposed mechanisms and risk factors involved in the complex interaction between antiseizure drugs and movement disorders. Antiseizure drugs mainly used to treat movement disorders are clonazepam, gabapentin, lacosamide, levetiracetam, oxcarbazepine, perampanel, phenobarbital, pregabalin, primidone, topiramate, and zonisamide. Antiseizure drugs that worsen or induce movement disorders are cenobamate, ethosuximide, felbamate, lamotrigine, phenytoin, tiagabine, and vigabatrin. Antiseizure drugs with a variable effect on movement disorders are carbamazepine and valproate while no effect on movement disorders has been reported for brivaracetam, eslicarbazepine, lacosamide, and stiripentol. Although little information is available on the adverse effects or benefits on movement disorders of newer antiseizure drugs (such as brivaracetam, cenobamate, eslicarbazepine, lacosamide, and rufinamide), the evidence collected in this review should guide the choice of antiseizure drugs in patients with concomitant epilepsy and movement disorders. Finally, these notions can lead to a better understanding of the mechanisms involved in the pathophysiology and treatments of movement disorders.

Evaluating the Longevity of Implantable Pulse Generator Used in Deep Brain Stimulation: A Systematic Review

Background and Aim: Deep Brain Stimulation (DBS) surgery is increasingly performed to treat movement disorders. In these patients, a rechargeable or non-rechargeable battery is placed under their subcutaneous chest after implantation of an electrode in the basal ganglia of the brain, which has different battery life. Methods and Materials/Patients: In this study, three databases, including PubMed, ScienceDirect, Scopus without time limit, and Google Scholar search engine were examined by two independent researchers. Results: In the initial search, a total of 338 data were found. Then, by reviewing the title and summary of articles, 17 articles were included in the study and then 13 articles were reviewed in full text. The results of the articles were divided into two subgroups of battery life related to the types or subtypes of movement disorders indicated by DBS and battery life related to the types of IPG models. Conclusion: Battery life in Parkinson’s movement disorder and tremor is longer than in dystonia. Also, the battery life of Soletra model is longer than Kinetra and Kinetra model is longer than Activa, and any battery replacement surgery reduces battery life.

Multiple Cervical Cutdowns of Scar Tissue to Treat Bowstringing After Deep Brain Stimulation: Description of Technique and Case Series

BACKGROUND: Deep brain stimulation (DBS) is widely used to treat movement disorders. One rare complication is bowstringing, the formation of scar tissue around the extension wires. This adverse effect can cause considerable pain or discomfort in the cervical region. Limited information is available about the best surgical technique to address this complication. OBJECTIVE: To present and describe a surgical technique (cervical cutdown [CCD]) to treat bowstringing. METHODS: We retrospectively reviewed records of DBS patients treated with CCD for bowstringing (August 1, 2011-February 28, 2020) to identify parameters that preceded the condition, evolution of the treatment technique, and patient outcomes. RESULTS: Nine patients (mean age, 61 years) underwent 10 CCD procedures for bowstringing. One patient required repeat CCD for retethering 10 months after the initial CCD. The mean time from DBS to presentation for initial bowstringing was 25 months. Six patients had undergone DBS surgery at our institution (0.6% incidence in 1068 cases). All 9 patients had 2 extension wires tunneled unilaterally. During each CCD, 2 to 4 cervical incisions were made. In 7 of the 10 cases, the internal pulse generator pocket was reopened; the extension wires were detethered in 4, and the internal pulse generator was replaced in 3. Six patients with follow-up (mean, 15 months) reported that their symptoms had improved ≥50%; 3 patients were lost to follow-up. CONCLUSION: A primary risk factor of bowstringing after DBS is likely the unilateral routing of 2 extension wires. CCD surgery is effective for symptomatic patients nonresponsive to conservative management.

Improving Deep Brain Stimulation Electrode Performance in vivo Through Use of Conductive Hydrogel Coatings.

Active implantable neurological devices like deep brain stimulators have been used over the past few decades to treat movement disorders such as those in people with Parkinson’s disease and more recently, in psychiatric conditions like obsessive compulsive disorder. Electrode-tissue interfaces that support safe and effective targeting of specific brain regions are critical to success of these devices. Development of directional electrodes that activate smaller volumes of brain tissue requires electrodes to operate safely with higher charge densities. Coatings such as conductive hydrogels (CHs) provide lower impedances and higher charge injection limits (CILs) than standard platinum electrodes and support safer application of smaller electrode sizes. The aim of this study was to examine the chronic in vivo performance of a new low swelling CH coating that supports higher safe charge densities than traditional platinum electrodes. A range of hydrogel blends were engineered and their swelling and electrical performance compared. Electrochemical performance and stability of high and low swelling formulations were compared during insertion into a model brain in vitro and the formulation with lower swelling characteristics was chosen for the in vivo study. CH-coated or uncoated Pt electrode arrays were implanted into the brains of 14 rats, and their electrochemical performance was tested weekly for 8 weeks. Tissue response and neural survival was assessed histologically following electrode array removal. CH coating resulted in significantly lower voltage transient impedance, higher CIL, lower electrochemical impedance spectroscopy, and higher charge storage capacity compared to uncoated Pt electrodes in vivo, and this advantage was maintained over the 8-week implantation. There was no significant difference in evoked potential thresholds, signal-to-noise ratio, tissue response or neural survival between CH-coated and uncoated Pt groups. The significant electrochemical advantage and stability of CH coating in the brain supports the suitability of this coating technology for future development of smaller, higher fidelity electrode arrays with higher charge density requirement.

Focused Ultrasound Mediated Opening of the Blood-Brain Barrier for Neurodegenerative Diseases.

The blood brain barrier (BBB) is an obstacle for the delivery of potential molecular therapies for neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Although there has been a proliferation of potential disease modifying therapies for these progressive conditions, strategies to deliver these large agents remain limited. High intensity MRI guided focused ultrasound has already been FDA approved to lesion brain targets to treat movement disorders, while lower intensity pulsed ultrasound coupled with microbubbles commonly used as contrast agents can create transient safe opening of the BBB. Pre-clinical studies have successfully delivered growth factors, antibodies, genes, viral vectors, and nanoparticles in rodent models of AD and PD. Recent small clinical trials support the safety and feasibility of this strategy in these vulnerable patients. Further study is needed to establish safety as MRI guided BBB opening is used to enhance the delivery of newly developed molecular therapies.

Physical Rehabilitation of Patients with Cerebral Blood Flow Acute Disorders in the Late Recovery Period

The purpose of this article is to substantiate, develop and evaluate the effectiveness of a physical rehabilitation comprehensive program using functional training method for patients with cerebral blood flow acute disorders in the late recovery period. The rehabilitation program focuses on improving the quality of life indicators according to the International Classification of Functioning, treating movement disorders and returning patients to their previ- ous functional level. The ascertaining experiment involved 73 patients. The primary diagnosis was the consequenc- es of cerebral blood flow acute disorders lasting for at least 6 months and not more than 9 months after a stroke. The physical rehabilitation comprehensive program was implemented amongst the patients of the experimental group (n=35) and the control group (n=38), the latter attending a standard physical rehabilitation course in a medical insti- tution. The statistical analysis revealed a great number of correlations at a significant level, which is explained by the connection between body structures and functions, activity and participation. The study proves the effectiveness of the proposed program as compared to the traditional approaches. It ascertains that using specialized methods based on functional training in post-stroke rehabilitation programs is the way to increase functional capacity and improve the adaptation of stroke patients.

Acute Movement Disorders in Childhood: A Cohort Study and Review of the Literature.

Acute movement disorders (AMD) are frequent in neurological and pediatric emergencies. Few studies analyzed AMD in children, none in Tunisia or other African country. The purpose of this study was to describe the peculiarities of AMD in a Tunisian pediatric population with a literature review. We conducted a retrospective descriptive study over 8 years including 80 children (sex ratio, 1.05; mean age of onset, 4.8 years) with AMD, followed in tertiary referral Child Neurology Department in North Tunisia. Acute movement disorders were mainly hyperkinetic (n = 67 with dystonia (n = 33; mostly due to inherited metabolic diseases (IMD) in 11; with status epilepticus in 10 children), chorea (n = 14; with Sydenham chorea in 5); myoclonus (n = 14; mostly with opsoclonus-myoclonus syndrome in 10) and tremor (n = 6; of posttraumatic origin in half). Hypokinetic movement disorder (MD) included acute parkinsonism in 5 children of infectious (n = 3), postinfectious (n = 1, malaria) and posttraumatic origin (n = 1). Mixed MD, found in 8 children, were mainly due to IMD in half of them, and to familial lupus in two. Paroxysmal MDs were seen in 2 children, one with multiple sclerosis and one of idiopathic origin. Psychogenic MDs were found in 7 patients mainly of dystonic type. Management of AMD comprised symptomatic treatment according to the phenomenology of the MD and causative treatment depending on its etiology. Our study illustrated the broad range of AMD in children and the wide spectrum of their etiologies. In our series, we described some exceptional findings and etiologies of AMD in children. These findings may denote a specific profile in of AMD in our country with predominant infectious, postinfectious, and IMD.

Movement Disorders in Multiple Sclerosis and Other Demyelinating Diseases: A Retrospective Review From a Tertiary Academic Center.

Movement disorders (MDs) have been described in demyelinating diseases (DDs). However, data is lacking in the effective treatment of these MD as well as in a potential correlation between DD lesions localization and the phenomenology of the MD and its response to treatment. Retrospective review of 185 patients with MD and DD seen at our center over a period of 7 years. Clinical imaging, medications, and therapeutic responses to both MD and DD treatments were reviewed. Of the 185 patients, 62 were excluded because of a diagnosis of spasticity without any other MD. One hundred twenty three patients with DD (75% female, age 48.8±12.8 y) had one or more MD. The most common MD was ataxia followed by isolated tremor. Forty-two patients (34%) received any treatment for MD, 29 (69%) of which responded at least partially to a first MD agent and 78.6% responded at least partially to a second or third agent. Responders to the first MD therapy were more likely to have a lesion in the basal ganglia or the cerebellum, and less likely to have a lesion in the brainstem or the spinal cord, but these results could be biased by a lower-than-expected frequency of tonic spasms in our series. No correlation between DD lesions localization and the phenomenology of the MD was discovered. MD are common in DD and are frequently overlooked or undertreated. MD in this sample have a 69% therapeutic response to a first trial. Greater awareness of potential therapeutic options is needed to decrease disability.