Dyskinesia Research Articles

Motor complications in Parkinson's disease: Ten year follow‐up study

Parkinson's disease (PD) can be symptomatically controlled with standard treatments; however, after a few years, this response typically declines and most patients develop motor complications. We carried out a prospective practice-based study to evaluate the evolution appearance and evolution of motor complications in 64 de novo PD patients over 5 years and in 38 PD patients over 10 years. We studied untreated patients from initial assessment at basal conditions and evaluated every 6 months thereafter with treatment (levodopa versus other drugs). The follow-up assessments were performed with the Unified Parkinson's Disease Rating Scale (UPDRS). At each assessment, patients were monitored regarding the development of dyskinesias, motor fluctuations, freezing, loss of postural reflexes, and cognitive impairment. We observed a significant improvement in UPDRS scores during the first year, then a progressive decline, more evident after the third year. Motor complications increased after the third year, and at the end of the survey (tenth year); drug-induced dyskinesias and motor fluctuations were experienced (71.1 and 94.7%, respectively). After the first decade, many complications arose from the non-levodopa-responsive features of the disease (cognitive impairment was present in 52.6% and gait freezing in 71.1%). Initial medication may influence medium-term complications but not long-term problems. Most long-term disabling problems of PD were related to non-levodopa-responsive features.

Does Continuous Dopaminergic Stimulation Reduce Dyskinesia Risk

With advancing disease and long-term levodopa therapy, most patients with Parkinson disease (PD) develop motor complications, such as dyskinesias and

Prevention of the complication of DBS procedures

Objective To study the complication of deep brain stimulation(DBS)procedures in the treatment of movement disorders. Method Retropective analysis of The complications and side effects in 278patients(531 sides)treated by DBS. Results Complications of DBS were related with operational procedures,choice and location of targets and the hardware. Operative - related complications were intracranial hemorrhage,seizures,leakage of cerebrospinal fluid. Targets related complications were dyskinesia,dysarthria,ptosis. Hardware -related complications were lead break, migration, machine failure. Conclusions The complications of DBS could be reduced by severely operative procedures,adaptable methods and exact programming. Key words: Deep brain stimulation; Complications; Prevention

Hyperbaric oxygen for children with dyskinetic cerebral palsy

Objective To evaluate the effectiveness and safety of hyperbaric oxygen (HBO) therapy as an adjunctive therapy for children with dyskinetic cerebral palsy. Methods Seventy-one children with dyskinetic cerebral palsy aged 6 mouths to 2 years were randomly assigned to a HBO group ( n = 35 ) or a control group ( n = 36).All children were given conventional rehabilitative treatment, but the children in the HBO group in addition received 40 sessions of HBO therapy. HBO was administered for 1 h with 85% ～ 90% oxygen at 1.4 atmospheres absolute pressure. All the treatments in both groups continued for 8 weeks. Gross motor function was evaluated with a gross motor function measure ( GMFM ), global motor performance was assessed with a psychomotor development index (PDI), and intelligence was assessed with a mental development index (MDI). Clinical assessments were done before and after treatment. At the same time, hearing impairment was measured using brainstem auditory evoked potentials (BAEPs) in the HBO group. Results All outcomes in both groups improved significantly over the course of study. The average improvement in GMFM in the control group was significantly greater than in the HBO group but other differences were not statistically significant. Hearing impairment developed in 8 children treated with HBO.Conclusion There was no evidence that HBO therapy improved the condition of children with dyskinetic cerebral palsy, and there is a risk of side effects with HBO therapy. Key words: Cerebral palsy; Dyskinesia; Hyperbaric oxygen; Rehabilitation

Application of chronoreflexotherapy for the management of biliary tract dysfunction

The objective of this work was to develop a scientifically sound rationale for the method of reflex correction of biliary tract dysfunction based on chronobiological data concerning functioning of the acupuncture points corresponding to biliary ducts. It was shown that patients presenting with biliary dyskinesia (i.e. forming desynchronism) experience a shift of both skin temperature and electrical resistance at the acupuncture points. The chronoreflexotherapeutic technique employed in this study makes it possible to rapidly restore disturbed biorhythms of functioning of the biliary system, normalize the motor-evacuating activity of the gallbladder, and eliminate clinical manifestations of the disease.

Levodopa in the treatment of Parkinson's disease: an old drug still going strong.

After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.

Juvenile levodopa-responsive Parkinsonism with early orobuccolingual dyskinesias and cognitive impairment

A 13-year old girl presented with slowly progressive rest tremor of the hands, bradykinesia, and rigidity. The symptoms improved with dopaminergic medications, but severe drug-induced dyskinesias developed early. She subsequently developed cognitive slowing and difficulty initiating saccadic eye movements. She went on to have deep brain stimulation surgery. Experts discuss the syndromal diagnosis and predict the underlying pathology. The pathological diagnosis is given and clinical learning points are considered.

Task force report on scales to assess dyskinesia in Parkinson's disease: Critique and recommendations

Drug-induced dyskinesia is a common phenomenon in Parkinson's disease (PD) and is often socially as well as physically disabling for patients. The Movement Disorders Society commissioned a task force to assess available clinical rating scales, critique their clinimetric properties, and make recommendations regarding their clinical utility. A task force composed six clinical researchers who systematically searched the literature for scales measuring dyskinesia in PD, evaluated the scales' previous use, performance parameters, and quality of validation data (if available). A scale was designated "Recommended" if the scale has been used in clinical studies beyond the group that developed it, has been specifically used in PD reports, and if clinimetric studies have established that it is a valid, reliable, and sensitive. "Suggested" scales met two of the above criteria and those meeting one were "Listed." Based on the systematic review, eight rating scales for dyskinesia that have either been validated or used in PD were identified. These were the Abnormal Involuntary Movement Scale (AIMS), The Unified Parkinson's Disease Rating Scale (UPDRS) part IV, the Obeso Dyskinesia Rating Scale, the Rush Dyskinesia Rating Scale, the Clinical Dyskinesia Rating Scale (CDRS), the Lang-Fahn Activities of Daily Living Dyskinesia Scale, the Parkinson Disease Dyskinesia Scale (PDYS-26), and the Unified Dyskinesia Rating Scale (UDysRS). Based on this review, at present two of the reviewed dyskinesia scales (AIMS and the Rush Dyskinesia Rating Scale) fulfill criteria for Recommended for use in PD populations, albeit weakly so; all of the remaining met criteria to be Suggested. However, the two most recent scales (PDYS-26 and UDysRS) have excellent clinimetric properties and appear to provide a reliable and valid assessment tool of dyskinesia in PD. If they are used successfully beyond the groups that developed them, both have the potential to be re-ranked as Recommended. As further testing of these scales in PD is warranted, no new scales are needed until the available scales are fully tested clinimetrically.

Korean ginseng extract attenuates reserpine-induced orofacial dyskinesia and improves cognitive dysfunction in rats

Reserpine-induced orofacial dyskinesia in rats is an animal model of tardive dyskinesia that has been linked with free radical generation and oxidative stress. In the present study, reserpine (1 mg kg−1, s.c.) was given to rats on days 1, 3 and 5 to induce orofacial dyskinesia, which is characterised by increased vacuous chewing and tongue protrusion. Sub-chronic treatment with Korean ginseng extract from day 1 to day 21 along with reserpine on days 1, 3 and 5 significantly and dose-dependently (100 and 200 mg kg−1) reduced reserpine-induced vacuous chewing movements and tongue protrusions. Reserpine-treated animals also showed poor retention of memory in the elevated plus maze paradigm. The sub-chronic Korean ginseng extract administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that repeated reserpine treatment significantly induced lipid peroxidation and decreased glutathione (GSH) levels in the brains of rats. Reserpine-treated rats also showed decreased levels of antioxidant defence enzymes, superoxide dismutase (SOD), and catalase. Sub-chronic administration of Korean ginseng extract dose-dependently and significantly reduced lipid peroxidation and restored decreased GSH levels by repeated reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The present study concludes that oxidative stress might play an important role in reserpine-induced abnormal oral movements, and Korean ginseng extract could be useful in the treatment of drug-induced dyskinesia and amnesia.

Deep brain stimulation of the subthalamic or entopeduncular nucleus attenuates vacuous chewing movements in a rodent model of tardive dyskinesia

Deep brain stimulation (DBS) has recently emerged as a potential intervention for treatment-resistant tardive dyskinesia (TD). Despite promising case reports, no consensus exists as yet regarding optimal stimulation parameters or neuroanatomical target for DBS in TD. Here we report the use of DBS in an animal model of TD. We applied DBS (100 μA) acutely to the entopeduncular nucleus (EPN) or subthalamic nucleus (STN) in rats with well established vacuous chewing movements (VCMs) induced by 12 weeks of haloperidol (HAL) treatment. Stimulation of the STN or EPN resulted in significant reductions in VCM counts at frequencies of 30, 60 or 130 Hz. In the STN DBS groups, effects were significantly more pronounced at 130 Hz than at lower frequencies, whereas at the EPN the three frequencies were equipotent. Unilateral stimulation at 130 Hz was also effective when applied to either nucleus. These results suggest that stimulation of either the EPN or STN significantly alleviates oral dyskinesias induced by chronic HAL. The chronic HAL VCM model preparation may be useful to explore mechanisms underlying DBS effects in drug-induced dyskinesias.

Presynaptic dopaminergic compartment determines the susceptibility to L-DOPA–induced dyskinesia in rats

Drug-induced dyskinesias in dopamine-denervated animals are known to depend on both pre- and postsynaptic changes of the nigrostriatal circuitry. In lesion models used thus far, changes occur in both of these compartments and, therefore, it has not been possible to dissect the individual contribution of each compartment in the pathophysiology of dyskinesias. Here we silenced the nigrostriatal dopamine neurotransmission without affecting the anatomical integrity of the presynaptic terminals using a short-hairpin RNA-mediated knockdown of tyrosine hydroxylase enzyme (shTH). This treatment resulted in significant reduction (by about 70%) in extracellular dopamine concentration in the striatum as measured by on-line microdialysis. Under these conditions, the animals remained nondyskinetic after chronic L-DOPA treatment, whereas partial intrastriatal 6-hydoxydopamine lesioned rats with comparable reduction in extracellular dopamine levels developed dyskinesias. On the other hand, apomorphine caused moderate to severe dyskinesias in both groups. Importantly, single-dose L-DOPA challenge in apomorphine-primed shTH animals failed to activate the already established abnormal postsynaptic responses. Taken together, these data provide direct evidence that the status of the presynaptic, DA releasing compartment is a critical determinant of both the induction and maintenance of L-DOPA-induced dyskinesias.

A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias

Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson’s disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE + BZ), LD + BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD + BZ or MPE + BZ at high (6 mg/kg) and medium (4 mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD + BZ at low doses (2 mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE + BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12 mg/kg and 20 mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD + BZ or MPE + BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD + BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug discoveries and novel treatment strategies in PD.

Brain-computer interface technology in the rehabilitation of central nerve system diseases

Objective To explore the prospects for applying a brain-computer interface system in the reha-bilitation of dyskinesia by testing the brain-electricity signals of spinal cord injury patients and stroke patients during motor imagery. Methods The brain-electricity signals of 5 healthy people, 4 spinal cord injury patients and 2 stroke patients were tested during motor imagery, and the results were analyzed with a computer. Results All of the 5 healthy people showed event-related synchronization and desynchronization (ERS/ERD) in the α and β bands in the motor related cortex. Three of the 4 spinal cord injury patents showed similar characteristics, and 1 showed ob-vious and stable characteristics, but the 2 stroke patients did not show meaningful characteristics. Conclusions Spinal cord injury patients have brain-electrlcity characteristics similar to those of healthy people when they are expe-riencing motor imagery, whilst in the affected hemisphere of stroke patients the brain-electricity characteristics are not similar to those of healthy people. Key words: Brain-computer interface; Motor imagery ; Stroke ; Spinal cord injury

Drs. Nelson and Papakostas Reply

Drs. Nelson and Papakostas Reply

A new biological marker isolated and characterizated in sputum from lung pathology patients: microparticles

Sputum is recognized as a very useful sampling method in Cystic Fibrosis (CF) for both research and clinical use aiding both the diagnosis and monitoring of lung disease inflammatory status. A great advantage of the technique is that it enables sampling of the airways in a non-invasive manner. We investigated on the presence and phenotype of microparticles (MPs) in the sputum, of acute and intermittent CF and Primary Ciliary Dyskinesia (PCD) adult patients. MPs are membrane vesicles that are released during cell activation and apoptosis. MPs have different biological effects depending on the cell from they originate. CF lung disease is characterized by massive neutrophil influx in the airways, their activation and eventually apoptosis. Spontaneous sputum, obtained from 21 CF patients (10 acute and 11 intermittent) and 7 patients with PCD, was liquefied with Sputasol. MPs were counted, visualized by electron microscopy, identified in the supernatants of treated sputum by cytofluorimetry and immunodecoration for leukocyte (CD11a), granulocyte (CD66b), and monocyte-macrophage (CD11b) antigens. Electron microscopy revealed that sputum MPs were in the 100-500 nm range and did not contain bacteria. CF sputa contained higher number of MPs in comparison with PCD sputa. CD66b and CD11a, but not CD11b, levels in MPs were significantly higher in CF than in PCD. Acute and intermittent patients presented significantly higher levels of CD11aand CD66b-expressing MPs respect to PCD patients. MPs are detectable in sputa obtained from CF patients and are predominantly of granulocyte origin. These findings are consistent with massive influx of neutrophils into CF airways and their accumulation on the surface of the airway epithelium. In this environment, neutrophils are activated by bacterial products, pro-inflammatory cytokines, and chemokines. Neutrophils undergo apoptosis, as normally happens in acute inflammation, but also postapoptotic necrosis, releasing toxic enzymes and oxygen radicals. MPs in CF sputa likely reflect both activation and apoptosis of neutrophils. The significantly less presence of granulocyte-derived MPs in PCD respect to CF patients, may be due to the fact that lung disease in PCD, although similar, is delayed in time as compared with CF. In CF airways, neutrophil-derived MPs could contribute to self-perpetuating inflammatory cycle, and may account for the exaggerated pro-inflammatory response of cells in CF patients. The MPs isolated from sputum could be a new non invasive methods and opens a new opportunity for the study of lung disease.

Drug safety monitoring in patients of movement disorders of a tertiary care hospital

Background:Movement disorders (MD) are neurological conditions that affect the speed, fluency, quality, and ease of movement and commonly include Parkinson’s disease, tremor and dystonias. Drugs are important causes of MD, and the incidence and prevalence of such disorders are possibly underappreciated because of the lack of recognition.Objectives:To assess the incidence of all adverse drug reactions (ADRs) and estimate the prevalence of drug-induced MD among patients attending the clinic.Materials and Methods:This prospective observational study was conducted at an outpatient referral MD clinic of a tertiary care hospital for 1 year. The demographic data, drug intake, diagnosis, and ADRs experienced by the subjects were recorded. Causality assessment was done by Naranjo’s scale.Results:Incidence of ADR among patients who attended this clinic was 19.7% (151 out of 768 patients experienced at least one ADR). A total of 299 ADRs were detected out of which 30.8% were gastrointestinal, 28.4% psychiatric, and 26% MD effects. The commonly implicated suspect drugs were levodopa (37.8%) and trihexyphenidyl (25.1%). The prevalence of drug-induced MD was 10.15% and drug-induced dyskinesias and dystonias were the most common.Conclusion:MDs are clinically important neurological disorders which are often caused by drugs and interestingly drugs used for its management are also associated with high incidence of ADRs. Hence these ADRs should be carefully monitored.

Study of ocular surface electromyography signal analysis

Test ocular surface electromyography signal waves and characteristic parameters to provide effective data for the diagnosis and treatment of ocular myopathy. Surface electromyography signals tests were performed in 140 normal volunteers and 30 patients with ophthalmoplegia. Surface electrodes were attached to medial canthi, lateral canthi and the middle of frontal bone. Then some alternate flashing red lamps were installed on perimeter to reduce the movement of eyeball. The computer hardware, software, and A/D adapter (12 Bit) were used. Sampling frequency could be selected within 40 kHz, frequency of amplifier was 2 kHz, and input short circuit noise was less than 3 microV. For normal volunteers, the ocular surface electromyography signals were regular, and the electric waves were similar between different sex groups and age groups. While for patients with ophthalmoplegia, the wave amplitude of ocular surface electromyography signals were declined or disappeared in the dyskinesia direction. The wave amplitude was related with the degree of pathological process. The characteristic parameters of patients with ophthalmoplegia were higher than normal volunteers. The figures of ocular surface electromyogram obtained from normal volunteers were obviously different with that from patients with ophthalmoplegia. This test can provide reliable quantized data for the diagnosis and treatment of ocular myopathy.

Santhera licenses novel dyskinesia therapy to Biovail

Santhera licenses novel dyskinesia therapy to Biovail

Non-pharmacological influencing factors of motor complications in Parkinson's disease: a systematic review

To make a systematic review of risk factors associated with motor complications in Parkinson's disease (PD). Medline, EMbase and Cochrane Database were used to search for prospective and retrospective studies on the factors associated with dyskinesia and motor fluctuations. Methodological quality was checked by two independent reviewers. Earlier age at onset, female gender and a long disease duration might be the risk factors of motor complications. More high-quality clinical trials are required to evaluate the factors associated with motor complications.

Ziprasidone-related oculogyric crisis in an adult

Introduction Drug-induced dyskinesias are common side-effects of first-generation antipsychotics (FGAs) but are not usually related to second-generation antipsychotics (SGAs). Oculogyric crisis (OGC) is a disabling acute dystonia that affects extra-ocular muscles usually resulting in an upward deviation of the eyes, which lasts from minutes to hours. Case report We describe an adult patient, previously exposed to an FGA, who developed OGC on 80 mg/day of ziprasidone. The movement disorder significantly improved after use of 1 mg/day of clonazepam without the need to switch to another SGA. Discussion The clinical features of the movement disorder of our patient meet the criteria for OGC. It is, sometimes, difficult to directly correlate a drug-induced dyskinesia to a SGA due to previous exposures to FGAs. The onset of OGC after exposure to ziprasidone without simultaneous use of other antipsychotic suggests a casual relationship between the former and the movement disorder. It is possible that previous use of an FGA was a risk factor for the development of OGC. Conclusion To the best of our knowledge, this is the first report of ziprasidone-related OGC in an adult patient. Physicians must be aware of its occurrence in order to improve care of patients treated with these agents.