Dyskinesia Research Articles

Lack variation of low slow-wave activity over time in the frontal region in NREM sleep may be associated with dyskinesia in Parkinson's disease.

Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.

West Syndrome due to ALG13 mutation presenting vigabatrin-associated reversible MRI signal changes and drug-induced dyskinesia

Heterozygous mutations in the asparagine-linked glycosylation 13 (ALG13) gene cause a rare genetic disorder that severely affects neurological development. Symptoms associated with ALG13 mutations include severe epilepsy and/or West syndrome (WS). Most cases reported in the literature describe typical characteristics of patients within whom de novo mutations have been identified. A 5-month-old girl with developmental delay and epileptic spasms, without dysmorphic features, is described. Electroencephalography (EEG) showed hypsarrhythmia, compatible with WS, but complementary examinations did not find an underlying etiology. Vigabatrin therapy was started, and then adrenocorticotropic hormone (ACTH) therapy was added. On follow-up, brain magnetic resonance imaging (MRI) revealed restricted diffusions compatible with vigabatrin-associated reversible MRI signal changes. As the spasms and hypsarrhythmia on EEG persisted, a second cycle of ACTH was performed, and then, the patient manifested a hyperkinetic movement, characteristic of drug-induced dyskinesia. Further investigation was carried out, and whole-exome sequencing revealed a de novo pathogenic variant in ALG13 gene. The current case report expands our knowledge of WS by considering a female patient with unspecific clinical features arising from an undefined subjacent etiology. This case also emphasizes the importance of a thorough work-up to determine the underlying genetic etiology and presents the challenges in the diagnostic investigation in clinical practice.

The 5-HT2A/2C inverse agonist nelotanserin alleviates L-DOPA-induced dyskinesia in the MPTP-lesioned marmoset.

Nelotanserin is a serotonin 2A and 2C (5-HT2A/2C) inverse agonist that was previously tested in the clinic for rapid-eye movement sleep behaviour disorder and psychosis in patients with Parkinson's disease (PD) dementia. Its effect on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia has however not been investigated. As 5-HT2A antagonism/inverse agonism is a validated approach to alleviate dyskinesia, we undertook the current study to evaluate the anti-dyskinetic potential of nelotanserin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset. Parkinsonism was induced in six common marmosets (Callithrix jacchus, three females and three males) that were then chronically treated with L-DOPA to induce dyskinesia. On experimental days, they were administered L-DOPA in combination with vehicle or nelotanserin (0.1, 0.3 and 1mg/kg) subcutaneously, in a randomised fashion. Dyskinesia and parkinsonism were rated post hoc by a blinded observer. In comparison to vehicle, the addition of nelotanserin 0.3 and 1mg/kg to L-DOPA diminished peak dose dyskinesia by 47% (P < 0.05) and 69% (P < 0.001). Nelotanserin 0.3 and 1mg/kg also reduced the severity of global dyskinesia, by 40% (P < 0.01) and 55% (P < 0.001), when compared to vehicle. Nelotanserin 0.1mg/kg did not alleviate peak dose or global dyskinesia severity. Nelotanserin had no impact on the anti-parkinsonian action of L-DOPA. Our results highlight that nelotanserin may represent an efficacious anti-dyskinetic drug and provide incremental evidence of the potential benefit of 5-HT2A/2C antagonism/inverse agonism for drug-induced dyskinesia in PD.

Drug-Induced Dyskinesia Treated with Korean Medicine: A Case Report

Drug-Induced Dyskinesia Treated with Korean Medicine: A Case Report

Role of Gamma Knife Radiosurgery in the Management of Functional Disorders - A Literature Review.

Role of radiosurgical lesioning in functional disorders has been restricted because of development of deep brain stimulation (DBS) techniques. However, many elderly patients with comorbidities and coagulation abnormalities may not be eligible for DBS. Radiosurgical lesioning may be a good alternative in such cases. The objective of the study was to review the role of radiosurgical lesioning for functional targets in common functional disorders. Literature reports pertaining to common disorders were reviewed. Disorders included are tremors (essential tremors, tremor-dominant Parkinson's disease [PD], multiple sclerosis [MS] related refractory tremors), Parkinson's disease (for rigidity, bradykinesia, drug-induced dyskinesias), dystonia, and obsessive-compulsive disorder (OCD). The most commonly performed procedure was ventral intermediate nucleus (VIM) lesioning for essential tremors and tremor-dominant PD, with about 90% patients demonstrating improvement. Intractable OCD with 60% responders is a promising indication. Other disorders are less commonly treated, with dystonia being the least commonly treated entity. Subthalamic nucleus (STN) and globus pallidus interna/posteroventral pallidum (GPi) lesioning are very rarely reported, and the available literature suggests caution due to high rates of adverse effects. Outcomes for radiosurgical lesioning for essential tremors (VIM) and OCD (anterior limb of internal capsule [ALIC]) are encouraging. Radiosurgical lesioning offers a lower immediate risk profile in patient population with several comorbidities; however, long-term adverse effects due to radiation are a concern, especially for STN and GPi lesioning.

Allergic Bronchopulmonary Aspergillosis in a Patient with Kartagener\'s Disease: An Unusual Association

Primary ciliary dyskinesia (PCD) is a congenital disorder characterized by abnormal ciliary motility with associated impaired mucociliary clearance. When PCD has associated situs inversus, it is known as Kartagener's disease. Due to recurrent sinopulmonary infections, patients of Kartagener's disease develop bronchiectasis. Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder characterized by exaggerated immune response to the fungus Aspergillus. Patients with ABPA also develop bronchiectasis in advanced stages. Here, we report a patient of Kartagener's disease who also had coexisting ABPA. We believe such an association has been reported in just a handful of cases. As Kartagener's disease can be easily diagnosed radiologically and bronchiectasis is a feature of Kartagener's disease, many of these patients do not undergo further evaluation. In reporting this rare occurrence, we believe many such associations will be revealed in future.

The impact on speech with different deep brain stimulation settings in Parkinson's disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by the progressive degeneration of the nigrostriatal dopaminergic pathway which affects movement initiation and maintenance, causing hypokinetic dysarthria in PD. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used to manage rigidity, bradykinesias and drug-induced dyskinesias. While STN DBS successfully manages many symptoms of PD, speech response has been widely reported as “no or negative impact”. The High-Frequency Setting (HFS) is more focused within the STN which is known to control appendicular symptoms. However, the unintentional HFS current spreading to adjacent brain areas, such as the corticospinal and corticobulbar tracts, was thought to contribute to the deterioration of axial symptoms, including speech. The Low-Frequency Setting (LFS) extends more dorsally and ventrally towards surrounding structures, hence does not show the same negative impact and may reduce the negative impact on the axial functions including speech. This double-blind, randomized perception study assesses the impact of two deep brain stimulation (DBS) settings (high-frequency stimulation and interleave-interlink dual-frequency paradigm) on speech produced by 20 patients with PD. The impact of the two testing conditions was different for different Syllable Types with significant negative correlation between the articulatory rate and articulatory accuracy.

Clinical correlates of movement disorders in adult Niemann-Pick type C patients measured via a Personal KinetiGraph

BackgroundNiemann-Pick type C (NPC) is an autosomal recessive progressive neurodegenerative disorder caused by mutations in the NPC1 or NPC2 genes. Patients with this disorder have variable phenotypic presentations that often include neuropsychiatric manifestations, cognitive decline, and movement disorders. There is considerable interpatient variation in movement disorders, with limited quantitative measurements describing the movements observed. Objective measurements using wearable sensors provide clinically applicable monitoring of patients with Parkinson’s disease, and hence may be utilized in patients with NPC.ObjectiveTo explore the relationship between objective measurements of movement obtained via the use of the Personal KinetiGraph (PKG) with the clinical information obtained via questionnaires and clinical rating tools of patients with Niemann-Pick type C.MethodsTwelve patients with Niemann-Pick type C were recruited who wore the PKG for 6 days during regular activities. A 6-day output was provided by the manufacturer, which provided bradykinesia (BK) and dyskinesia (DK) scores. BK and DK scores were further divided into their interquartile ranges. A fluctuation score (FDS), percentage time immobile (PTI), and percent time with tremors (PTT) were also provided. Clinical assessments included Abnormal Involuntary Movement Scale (AIMS), Epworth Sleepiness Score (ESS), Falls, Neuropsychiatric Unit Assessment Tool (NUCOG), Parkinson’s disease questionnaire (PDQ), and modified Unified Parkinson’s Disease Rating Scale (UPDRS) which were performed over telehealth within 2 weeks of PKG use. Pearson’s correlation analyses were utilized to explore the relationship between DK and BK quartiles and clinical measures.ResultsWe found bradykinesia to be a feature among this cohort of patients, with a median BKS of 22.0 (7.4). Additionally, PTI scores were elevated at 4.9 (8.2) indicating elevated daytime sleepiness. Significant correlations were demonstrated between BK25 and Falls (r = − 0.74, 95% CI = [− 0.95, − 0.08]), BK50 and Falls (r = − 0.79, 95% CI = [− 0.96, − 0.19]), and BK75 and Falls (r = − 0.76, 95% CI = [− 0.95, − 0.11]). FDS correlated with PDQ (r = − 0.7, 95% CI = [− 0.92, − 0.18]), UPDRS IV (r = − 0.65, 95% CI = [− 0.90, − 0.09]), UPDRS (r = − 0.64, 95% CI = [− 0.9, − 0.06]), and AIMS (r = − 0.96, 95% CI = [− 0.99, − 0.49]). DK25 in comparison with NUCOG-A (r = 0.72, 95% CI = [0.17, 0.93]) and DK75 in comparison with NUCOG (r = 0.64, 95% CI = [0.02, 0.91]) and NUCOG-A (r = 0.63, 95% CI = [0.01, 0.90]) demonstrated significant correlations. Additionally, duration of illness in comparison with PTI (r = 0.72, 95% CI = [0.22, 0.92]) demonstrated significance.ConclusionsUtilization of PKG measures demonstrated that bradykinesia is under recognized among NPC patients, and the bradykinetic patients were less likely to report concerns regarding falls. Additionally, the FDS rather than the DKS is sensitive to the abnormal involuntary movements of NPC—reflecting a differing neurobiology of this chorea compared to levodopa-induced dyskinesias. Furthermore, dyskinetic individuals performed better in cognitive assessments of attention which may indicate an earlier timepoint within disease progression.

Interleukin-6 in schizophrenia is associated with negative symptoms, side effects of therapy and smoking: results of a pilot study

Interleukin-6 (IL-6) is one of the most important pro-inflammatory markers with immunomodulatory activity associated with schizophrenia. The possible involvement of interleukin-6 in the etiopathogenesis of schizophrenia and the development of different clusters of symptoms remains debatable; the relationship between an increase in interleukin-6 and a number of possible confounding factors, including smoking, has not yet been studied. The aim of this work was the pilot evaluation of the serum IL-6 level in patients with schizophrenia compared with healthy controls, as well as its association with clinical symptoms, socio-demographic factors and smoking. Materials and methods: 43 patients with schizophrenia and 24 healthy volunteers were examined. The determination of IL-6 was carried out by enzyme immunoassay. All patients were assessed using the Positive and Negative Schizophrenia Syndrome Scale (PANSS), The UKUSERS-Clin Therapeutic Side Effects Scale (UKU), Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), Barnes Akathisia Scale (BARS), Personal and Social Functioning Scale (PSP). Results: In patients with schizophrenia in a Russian sample, serum IL-6 levels were significantly associated with smoking status (p = 0.0017), the severity of negative symptoms and symptoms of the PANSS general psychopathology scale (p=0.014 and p=0.038, respectively), disorders of personal and social functioning (PSP, p=0.011), as well as side effects measured using the UKU scale (general, p=0.038, 0041 and extrapyramidal, p=0.018), as well as drug-induced parkinsonism (p=0.043), dyskinesia (p=0.0084) and akathisia (p=0.043). All scores are worse in patients with nicotine addiction. The occurrence of extrapyramidal symptoms (EPS) in response to standard doses of antipsychotics (AP) can serve as a clinical marker of possible immune-inflammatory disturbances in patients with schizophrenia, and the smoking status can act as a provocing factor for increasing of latent inflammation. Replication of the study is required to confirm the findings.

An insight into reactivity and bioactivity properties of quorum sensing peptides against PDE10A: a computational peptidology approach.

Peptides are currently the most promising lead molecules. Quorum sensing peptides have a variety of structural features and are regularly exposed to post-translational modifications. Antiparkinsonian drugs lose their efficacy after a long period of use, and patients develop motor problems such as drug-induced dyskinesia (DIDs). The interaction between PDE10A and cAMP is necessary for dopamine neurotransmission and may play a role in Parkinson's disease pathogenesis. cAMP and cGMP are cyclic nucleotides that act as secondary messengers in the signal transduction pathway, influencing a range of CNS activities. PDE enzymes hydrolyze phosphodiester bonds to break down cAMP and cGMP, allowing them to control intracellular levels of these second messengers effectively. PDE expression, and hence cyclic nucleotide levels and their downstream targets, may change with age and in numerous age-related illnesses, including Parkinson's disease, according to mounting evidence. At the peak of dyskinesias, cyclic nucleotide levels were lower, and using phosphodiesterase inhibitors before antiparkinsonian medicines reduced the severity of dyskinesias. In a recent study, PapRIV was found to have the ability to activate BV-2 microglia cells, indicating that this quorum sensing peptide may play a role in gut-brain contact. As a result of the current in silico work, mainly focused on QSPs as a lead molecule for inhibiting PDE10A, the SRNAT QSP sequence has been a potent molecule in molecular docking and molecular dynamics simulations. Furthermore, we can test the efficiency of therapeutic components in vitro and in vivo utilizing this computational approach against PDE10A.

Gender Differences in Levodopa Pharmacokinetics in Levodopa-Naïve Patients With Parkinson's Disease.

BackgroundLevodopa (LD) is the most effective drug in the treatment of Parkinson’s disease (PD). Unfortunately, prolonged use of LD leads to complications, mainly motor/non-motor fluctuations (MNMF) and dyskinesias (DYS). Women seem more prone to develop such LD-related complications. Nonetheless, there is a paucity of prospective studies examining gender-related predictors of MNMF and DYS. Among several factors, which concur with a very complex scenario, changes in LD pharmacokinetics influence the drug’s effectiveness. The present study aimed to assess gender-related differences in LD pharmacokinetics in patients with PD at their first-ever intake of LD.Materials and MethodsThis is a multicentric study enrolling patients with PD, who were LD-naïve and received a single dose of LD/benserazide (100/25 mg) formulation. All participants gave their written informed consent, and the study was approved by the local Ethics Committees. To measure plasma LD concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, t1/2), fasting blood samples were collected before drug intake and then at 8-time points until 260 min. LD concentrations were measured by ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Multiple linear regression analyses were performed to identify the predictors of the parameters.ResultsThirty-five patients (16 women and 19 men) were consecutively enrolled. Area under curve (AUC) and maximum plasma concentration (Cmax) were significantly higher in women than men (p = 0.0006 and p = 0.0014, respectively). No statistically significant difference was found regarding Tmax and t1/2. Multiple linear regression analyses revealed that female sex (β = 1.559116, 95% CI 0.8314479 2.286785; p < 0.0001) and body mass index (BMI) (β = −0.0970631, 95% CI −0.1733004 −0.0208258; p = 0.014) significantly predicted AUC. Only female sex significantly predicted Cmax (β = 1,582.499, 95% CI 731.581 2,433.417; p = 0.001). Moreover, only BMI significantly predicted t1/2 (β = 0.0756267, 95% CI 0.0143407 0.1369126; p = 0.017). Stratifying by gender, BMI was confirmed to significantly predict t1/2 in women (β = 0.1300486, 95% CI 0.0172322 0.242865; p = 0.027), but not in men.ConclusionThis study provides novel insights on gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD.

Dopamine D2L Receptor Deficiency Alters Neuronal Excitability and Spine Formation in Mouse Striatum.

The striatum contains several types of neurons including medium spiny projection neurons (MSNs), cholinergic interneurons (ChIs), and fast-spiking interneurons (FSIs). Modulating the activity of these neurons by the dopamine D2 receptor (D2R) can greatly impact motor control and movement disorders. D2R exists in two isoforms: D2L and D2S. Here, we assessed whether alterations in the D2L and D2S expression levels affect neuronal excitability and synaptic function in striatal neurons. We observed that quinpirole inhibited the firing rate of all three types of striatal neurons in wild-type (WT) mice. However, in D2L knockout (KO) mice, quinpirole enhanced the excitability of ChIs, lost influence on spike firing of MSNs, and remained inhibitory effect on spike firing of FSIs. Additionally, we showed mIPSC frequency (but not mIPSC amplitude) was reduced in ChIs from D2L KO mice compared with WT mice, suggesting spontaneous GABA release is reduced at GABAergic terminals onto ChIs in D2L KO mice. Furthermore, we found D2L deficiency resulted in reduced dendritic spine density in ChIs, suggesting D2L activation plays a role in the formation/maintenance of dendritic spines of ChIs. These findings suggest new molecular and cellular mechanisms for causing ChIs abnormality seen in Parkinson’s disease or drug-induced dyskinesias.

Lithium-associated movement disorder: A literature review.

In 1949, Cade described “sedative effects” after injecting guinea pigs intraperitoneally with lithium (LTM) carbonate. Based on his experiments, he began treating psychiatric patients with LTM. This literature review aims to evaluate the clinical epidemiological profile, pathological mechanisms, and management of LTM-associated movement disorder (MD). Relevant reports in six databases (Excerpta Medica, Google Scholar, Latin American and Caribbean Health Sciences Literature, Medline, Scientific Electronic Library Online, and ScienceDirect) were identified and assessed by two reviewers without language restriction from 1949 to 2021. A total of 250 reports containing 1100 individuals who developed MD associated with LTM were identified. The MDs encountered 148 parkinsonism (PKN), 114 dyskinesia (DKN), 97 myoclonus, 22 dystonia (DTN), 20 Creutzfeldt–Jakob-like syndrome, 11 akathisia, 10 restless legs syndrome (RLS) symptoms, 6 tics, 5 cerebellar syndromes, and 3 stuttering. In the subgroup of cases not clearly defined, there were 320 individuals with extrapyramidal symptoms, 135 with DTN, 37 with DKN, 24 with PKN, and 7 with RLS. Other 141 individuals were only described as presenting an abnormal involuntary movement without further explanation. The mean age was 53.06 years (standard deviation [SD]: 15.64) and the predominant sex was female, i.e., 56.20% (154/274). The mean LTM dose was 963.03 mg/day (SD: 392.03). The mean serum LTM level was 1.53 mEq/L (SD: 1.08). The median onset time was 3 months (1 day to 40 years). The mean recovery time was 0.94 months (SD: 0.87). 45.94% had a full recovery. LTM-induced MD was extensively reported in the literature. Only general terms were used in the majority of the reports. LTM polytherapy probably affected the identification of the MD cause.

Праміпексол пролонгованого вивільнення — нові можливості тривалої дофамінергічної стимуляції при хворобі Паркінсона

Найважливішим підходом до дофамінергічної стимуляції при хворобі Паркінсона (ХП) є застосування агоністів дофамінових рецепторів (АДР). Порівняно з препаратами леводопи АДР характеризуються меншим ризиком розвитку лікарських дискінезій і моторних флуктуацій, відсутністю необхідності метаболізації в головному мозку й встановленим в експерименті нейропротективним потенціалом. Одним з найбільш ефективних препаратів цієї групи є праміпексол — синтетичне похідне бензотіазолу (тетрагідробензотіазол). Праміпексол є потужним агоністом D2-рецепторів з максимальною спорідненістю до підтипу D3-рецепторів. Стимуляція D2-рецепторів базальних гангліїв забезпечує ефект препарату щодо рухових проявів захворювання, у той час як стимуляція D3-рецепторів лімбічної системи зменшує немотор-ні прояви, у тому числі позитивно впливає на нейропсихологічний статус і зменшує ступінь вираженості депресивного синдрому у хворих із ХП. Ефективність праміпексолу доведена численними дослідженнями як на ранніх стадіях ХП — як монотерапії, так і на розгорнутих стадіях — у поєднанні з препаратами леводопи. Із розвитком захворювання схема його лікування ускладнюється за рахунок збільшення кількості прийнятих препаратів і кратності їх прийому. Це неминуче створює проблему недостатньої прихильності пацієнтів до лікування. У зв’язку з цим розроблена нова лікарська форма праміпексолу — праміпексол пролонгованої дії, що забезпечує його тривале вивільнення й допускає одноразовий прийом протягом дня. Це не тільки робить лікування хворого більш зручним, але й покращує прихильність пацієнтів до лікування, підвищує довгострокову ефективність терапії. Крім того, при повільному вивільненні праміпексолу протягом доби досягається більш стабільна його концентрація в крові, що може забезпечити кращу переносимість і ефективний контроль симптомів захворювання протягом усього дня (як у денний, так і в нічний час).

Drug-Induced Tardive Dyskinesia

Drug-induced movement disorders could be classified into acute, subacute, and chronic based on the time of occurrence. Tardive dyskinesia (TD) is one of the most frequent long-term drug-induced movement disorders. Delay in treatment often caused TD to be irreversible. In this review, we will discuss TD in-depth to enhance clinician knowledge regarding the diagnosis, prevention, and comprehensive management of patients with TD. Keywords: tardive dyskinesia, movement, disorder, antipsychotic.

Comparison of the Parkinson’s KinetiGraph to off/on levodopa response testing: Single center experience

Background and objectiveLevodopa off/on testing is frequently performed to assess medication response in patients with Parkinson’s disease (PD) as an aid in determining best medical management or potential surgical candidacy. The Parkinson’s Kinetigraph (PKG) is a wearable device which generates tremor, bradykinesia (BKS) and dyskinesia (DKS) scores representing motor symptoms over a six-day period. In this study, we compared off/on testing with PKG motor scores. MethodsPatients were enrolled as part of an observational study: Assessing the Longitudinal Signs in PD, a three-year study evaluating clinical and biomarker evolution in patients with PD taking levodopa. Patients underwent off/on testing at baseline and 6-month visits. A greater than 30% improvement between off and on MDS-Unified Parkinson’s Disease Rating Scale scores was considered a robust response. After each visit, patients wore the PKG for 6 days. A bradykinesia score (BKS) greater than 26 and dyskinesia score (DKS) greater than 9 were considered poorly controlled bradykinesia and dyskinesia, respectively. ResultsThe median BKS at the baseline and 6-month visits were 27.15 and 27.55, respectively, despite a robust median off/on improvement at both visits. In addition, 10/18 (66%) and 7/13 (53.8%) patients with robust off/on improvement at the baseline and 6-month visits, respectively, demonstrated a BKS > 26 or DKS > 9. ConclusionA robust off/on response during a clinic visit does not necessarily reflect adequately controlled motor symptoms. The PKG, by virtue of its continuous recording of motor movements, may provide additional clinically relevant data on motor symptoms which may be useful for prospective observational studies.

Effect of Varenicline on Tardive Dyskinesia: A Pilot Study.

ObjectiveAlthough evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia.MethodsThree schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1 mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient.ResultsVarenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia.ConclusionIn contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.

Parkinson's Disease: Carbidopa, Nausea, and Dyskinesia [Retraction

[This retracts the article DOI: 10.2147/CPAA.S72234.].

Valproate-associated Movement Disorder: A Literature Review.

Valproate (VPA) was first synthesized in 1882, but it was only in the early 1960s that its anticonvulsant properties were discovered. The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of VPA-associated movement disorder (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 138 reports containing 362 cases of subjects who developed a MD secondary to VPA were reported. The MD identified were parkinsonism (PKN) (252), myoclonus (MCL) (54), dystonia (DTN) (17), dyskinesia (DKN) (16), stutters (4), tics (3), akathisia (AKT) (1). In the not clearly defined group, 15 extrapyramidal symptoms, 3 AKT, 2 DTN, 1 rigidity, 1 unstable gait were assessed. The mean and median age was 55.8 (SD: 16.58) and 61 years (range: 4-87 years). The most common VPA-indication was epilepsy, and 51.36% were males. The mean and median time from the VPA start to the MD onset was 32.75 (SD: 30.05) and 21.15 months (range: 1 day - 20 years). The mean and median time from the VPA withdrawal until the MD recovery was 2.89 (SD: 2.79) and 3 months (1 day - 12 months). The most common management was drug withdrawal. A complete recovery was obtained in 80.61%. VPA-associated MD was extensively reported in the literature. PKN was the most well-described. Future studies need to clearly report the clinical history of the patient, considering the full investigation of other adverse events during their entire life.

Amantadine for the Treatment of Parkinson’s Disease and its Associated Dyskinesias

Amantadine for the Treatment of Parkinson’s Disease and its Associated Dyskinesias