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Activation of metabotropic glutamate 2 (mGlu2) receptors is a potential novel therapeutic approach for the treatment of parkinsonism. Thus, when administered as monotherapy or as adjunct to a low dose of L‐3,4‐dihydroxyphenylalanine (L‐DOPA), the mGlu2 positive allosteric modulator (PAM) LY‐487,379 alleviated parkinsonism in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐lesioned primates. Here, we sought to investigate the effect of biphenyl‐indanone A (BINA), a highly selective mGlu2 PAM whose chemical scaffold is unrelated to LY‐487,379, to determine if a structurally different mGlu2 PAM would also confer anti‐parkinsonian benefit. In monotherapy experiments, MPTP‐lesioned marmosets were injected with either vehicle, L‐DOPA/benserazide (15/3.75 mg/kg, positive control) or BINA (0.1, 1, 10 mg/kg). In adjunct to a low L‐DOPA dose experiments, MPTP‐lesioned marmosets were injected with L‐DOPA/benserazide (7.5/1.875 mg/kg) in combination with vehicle or BINA (0.1, 1, 10 mg/kg). Parkinsonism, dyskinesia and psychosis‐like behaviours (PLBs) were then quantified. When administered alone, BINA 1 and 10 mg/kg decreased parkinsonism severity by ~22% (p < 0.01) and ~47% (p < 0.001), when compared with vehicle, which was comparable with the global effect of a high L‐DOPA dose. When administered in combination with a low L‐DOPA dose, BINA 1 and 10 mg/kg decreased global parkinsonism by ~38% (p < 0.001) and ~53% (p < 0.001). BINA 10 mg/kg decreased global dyskinesia by ~94% (p < 0.01) and global PLBs by ~92% (p < 0.01). Our results provide additional evidence that mGlu2 positive allosteric modulation elicits anti‐parkinsonian effects. That this benefit is not related to a particular chemical scaffold suggests that it may be a class effect rather than the effect of a specific molecule. [ABSTRACT FROM AUTHOR]

Background: Pain fluctuations are a characteristic phenomenon in advanced Parkinson's disease (PD), but their temporal association with motor and non-motor symptom (NMS) fluctuations remains largely enigmatic. Moreover, data on their importance for disease severity perception and health-related quality-of-life (hr-QoL) is limited. Objective: To dissect pain fluctuations with respect to pain type and frequency patterns, and their association with motor and non-motor fluctuations. Methods: Prospective observational cohort study in advanced PD assessing symptom fluctuations by simultaneous hourly ratings using the PD Home diary (Off, On, Dyskinetic state), a pain diary (assessing 9 pain types) and a non-motor diary (10 key NMS) based on validated instruments. Results: Forty-seven out of 55 eligible participants with fluctuating PD (51% men, median age 65, median disease duration 10 years) had sufficient datasets (>95% of hours) from 2 consecutive days. Pain was reported in 35% of waking hours with clear circadian rhythm peaking in early morning Off periods and clustering during motor Off state (49% of Off state hours with pain). Main NMS co-fluctuating with pain were "Fatigue" and "Inner Restlessness". Simultaneous assessment of global disease severity by participants revealed that pain was associated with worse disease severity only in motor On and Dyskinetic state but not in Off state, which translated into significant correlations of daily pain times with hr-QoL only during motor On and Dyskinetic state. Conclusions: Aside from treating motor Off periods, specific recognition of pain particularly during motor On and Dyskinetic state comprises an important aspect for disease management in advanced PD. Plain Language Summary: Oscillations of the frequency and severity of pain over the day (also called pain fluctuations) are common in advanced Parkinson's disease (PD). However, their relationship with oscillations of motor and other non-motor symptoms remains unclear. Moreover, only very little data exists on how pain impacts disease severity perception and quality of life for the patients. The present study thus aimed to better understand pain fluctuations and their association with motor and non-motor symptoms in advanced PD. We conducted a prospective observational cohort study in advanced PD patients. Participants rated their symptoms hourly on two consecutive days using three diaries: the PD Home diary (for motor fluctuations), a pain diary (assessing several pain types), and a non-motor diary covering 10 key non-motor symptoms. Pain occurred during 35% of waking hours with a clear circadian rhythm peaking in the early morning and clustering during motor "Off" states as characterized by pronounced motor symptoms. The main non-motor symptoms associated with pain were "Fatigue" and "Inner Restlessness." Interestingly, pain severity correlated with health-related quality of life only during motor "On" state (defined as a state with good mobility and motor function) and "Dyskinetic" state characterized by the occurrence of involuntary movements, but not during motor "Off" periods. In conclusion, in managing advanced PD, recognizing pain during motor "On" and Dyskinetic states is crucial beyond just addressing motor "Off" periods. This understanding can significantly impact disease management and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

There is mounting evidence that positive allosteric modulation of metabotropic glutamate type 2 receptors (mGluR2) is an efficacious approach to reduce the severity of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, psychosis-like behaviours (PLBs), while conferring additional anti-parkinsonian benefit. However, the mGluR2 positive allosteric modulators (PAMs) tested so far, LY-487,379 and CBiPES, share a similar chemical scaffold. Here, we sought to assess whether similar benefits would be conferred by a structurally-distinct mGluR2 PAM, biphenylindanone A (BINA). Six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets exhibiting dyskinesia and PLBs were administered L-DOPA with either vehicle or BINA (0.1, 1, and 10 mg/kg) in a randomised within-subject design and recorded. Behaviour was analysed by a blinded rater who scored the severity of each of parkinsonism, dyskinesia and PLBs. When added to L-DOPA, BINA 0.1 mg/kg, 1 mg/kg, and 10 mg/kg all significantly reduced the severity of global dyskinesia, by 40%, 52% and 53%, (all P < 0.001) respectively. BINA similarly attenuated the severity of global PLBs by 35%, 48%, and 50%, (all P < 0.001) respectively. Meanwhile, BINA did not alter the effect of L-DOPA on parkinsonism exhibited by the marmosets. The results of this study provide incremental evidence of positive allosteric modulation of mGluR2 as an effective therapeutic strategy for alleviating dyskinesia and PLBs, without hindering the anti-parkinsonian action of L-DOPA. Furthermore, this therapeutic benefit does not appear to be confined to a particular chemical scaffold. [ABSTRACT FROM AUTHOR]

Objective To observe the ameliorative effects of the self-formulated Danxing Zhichan decoction on the dyskinesia and neuronal damage in mice with Parkinson's disease and to explore the mechanism. Methods Forty-eight male C57BL/6 mice were randomly divided into the control group, model group, positive control group, and low-, medium- and high-dose Danxing Zhichan decoction groups, with eight mice in each group. The PD models were prepared by gavage with rotenone solution in all groups except the control group, and mice in the control group were given saline by gavage once a day for 28 d. After successful modeling, mice in the low-, medium- and high-dose Danxing Zhichan decoction groups were given Danxing Zhichan decoction 11. 1,22. 2 and 44. 4 g/(kg·d) by gavage, and mice in the positive control group were given Medoba Suspension 112. 5 mg/(kg·d) by gavage, and mice in the control group and model group were given 0. 4 mL normal saline by gavage once a day for 28 d. The motor ability of mice was observed using the grid test and the rotating rod test, and the α synaptic nuclear proteins (α-Syn) in the nigral region of the midbrain was detected by immunohistochemistry, and the Toll-like receptor 4(TLR4), nuclear factor-κB (NF-κB) p65, and α-Syn protein were detected by Western blotting. Results Mouse movement latency was as follows: control group < positive control group, medium-dose Danxing Zhichan decoction group < high-dose Danxing Zhichan decoction group < low-dose Danxing Zhichan decoction group and model group, and the rotating rod holding time was as follows: control group > positive control group, medium-dose Danxing Zhichan decoction group > high-dose Danxing Zhichan decoction group > low-dose Danxing Zhichan decoction group and model group (all P<0. 05). The proportion of a-Syn positive cells in the substantia nigra region of mouse midbrain was as follows: control group < positive control group, medium-dose Danxing Zhichan decoction group < high-dose Danxing Zhichan decoction group < low-dose Danxing Zhichan decoction group and model group (all P<0. 05), and the TLR4, NF-κB p65 and a-Syn protein expression were as follows: control group < positive control group, mediumdose Danxing Zhichan decoction group < high-dose Danxing Zhichan decoction group < low-dose Danxing Zhichan decoction group and model group (all P<0. 05). Conclusion Self-formulated Danxing Zhichan decoction can alleviate the dyskinesia and neuronal damage in PD mice, and its mechanism may be related to the regulation of TLR4/NF-κB pathway and thus inhibiting the central neuroinflammation. [ABSTRACT FROM AUTHOR]

Objective: 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. Method s : 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD). Objectives: We performed a meta‐analysis on randomized clinical trials (RCTs) that compared early‐ versus delayed‐start treatment with levodopa in PD. Methods: A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non‐randomized comparisons from follow‐up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias. Results: Seven studies with a total of 1149 patients (636 in the early‐start group and 513 in the delayed‐start) were included in our analysis. There was no difference between groups regarding motor complications (OR 1.39; 95% CI: 0.68–1.72; P = 0.37) or dyskinesias (OR 1.52; 95% CI: 0.90–2.57; P = 0.11). Motor fluctuations occurred less frequently in the early‐start group (OR 0.70; 95% CI: 0.52–0.95; P = 0.02). Nonetheless, on subgroup analysis of dopamine agonists, rate of dyskinesias was smaller in the delayed‐start group (OR 1.82; 95% CI: 1.08–3.07; P = 0.03). Conclusions: Delaying treatment with levodopa does not seem to prevent levodopa‐related motor complications in PD. Adjunct treatment with dopamine agonists may reduce the need for higher doses of levodopa and thus reduce the risk for dyskinesias but this practice is often associated with a higher frequency of adverse effects related to dopamine agonists. [ABSTRACT FROM AUTHOR]

De Vivo disease is a rare genetic disorder associated with glucose transporter type 1 (GLUT1) deficiency. We provide a review of publications describing various clinical manifestations of this syndrome, including the combination of epilepsy with choreic hyperkinesis. The seizures related to De Vivo disease are resistant to basic antiepileptic therapy. The ketogenic diet is suggested as the main treatment method. We present our own clinical observation describing an 18-years old male patient, who had myoclonic-astatic seizures and atactic manifestations such as impaired movements coordination and walking instability, which first appeared at the age of 1.5 years. Due to therapy with valproic acid drugs, seizures persisted with a frequency of up to 5 times a month. From the age of 17, involuntary violent irregular movements of trunk and limb muscles emerged, occurring at a fast pace. The patient underwent a comprehensive examination; as a result, the diagnosis of De Vivo disease was verified. By prescribing proper antiepileptic therapy and ketogenic diet, it was possible to stabilize the patient's condition and stop De Vivo disease-related manifestations of epilepsy and hyperkinetic disorder. We pay attention to the differential diagnosis of conditions characterized by epileptic seizures, mental retardation and violent movements, as well as to the diagnosis and management tactics of patients with De Vivo disease. Unfortunately, not all patients with this pathology receive adequate pathogenetic and symptomatic therapy often undergoing numerous hospitalizations, since the major cause underlying such symptoms, namely GLUT1 deficiency, is not diagnosed.

Belly dancer’s dyskinesia (BDD) is characterized by involuntary abdominal wall movements that are rhythmic, repetitive, and dyskinetic. The present study aims to review BDD’s etiology, pathophysiology, and management. We searched six databases to locate existing reports on BDD published from 1990 to October 2023 in electronic form. A total of 47 articles containing 59 cases were found. The majority of the patients affected by BDD were female, accounting for 61.01% (36/59) of the cases. The mean and median ages were 49.8 (standard deviation: 21.85) and 52 years (range: 7–85), respectively. The BDD was unilateral in only 3.38% (2/59). The most commonly reported causes associated with BDD were 17 idiopathic, 11 drug-induced, 11 postsurgical procedures, 5 pregnancies, and 4 Vitamin B12 deficiencies. BDD is a diagnosis of exclusion, and other more common pathologies with similar presentation should be ruled out initially. Differential diagnostic reasoning should include diaphragmatic myoclonus, cardiac conditions, truncal dystonia, abdominal motor seizures, propriospinal myoclonus, and functional or psychiatric disorders.

Background: Childhood gratification syndrome (CGS) refers to self-stimulatory or masturbatory behaviors in children, which may have an onset as early as in infancy (IGS). Aim: The aim of this review is to understand the various clinical manifestations of CGS/IGS and their clinical differentiation from commonly misdiagnosed neurological and physical illnesses and to formulate a preliminary approach to their diagnosis and management. Methods: This narrative review is based on a search of literature over the past 50 years (1972–2022) in three online databases (PubMed/Medline, Embase, and Google Scholar). Results: The behaviors are episodic, occurring for brief periods, involving posturing, stereotypical limb movements, pubic pressure with autonomic hyperactivity, and postepisodic lethargy. They mimic seizures, movement disorders, abdominal pain, and tics. The paper also highlights the gap in the current knowledge to guide future research in the area. CGS usually represents nonpathological “pleasure-seeking” habits of childhood, but at times, it may become problematic for the child and his family. A careful history and videotape analysis of the events confirms the diagnosis and behavioral therapy with parental reassurance as the mainstay of treatment. Conclusion: A better understanding and clinical awareness of the CGS are necessary to prevent misdiagnosis and delay in appropriate intervention.

Background and Objectives: Vertical rhythmic dyskinetic movements that are primarily drug-induced and affect solely the jaw, mouth, and lips without involving the tongue have been historically described as "rabbit" syndrome (RS). Evidence on the unique features and implications of this disorder remains limited. This literature review aims to evaluate the clinical–epidemiological profile, pathological mechanisms, and management of this movement disorder. Materials and Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction published between 1972 and 2024. Results: A total of 85 articles containing 146 cases of RS were found. The mean frequency of RS among adults in psychiatric hospitals was 1.2% (range 0–4.4%). The mean age of affected patients was 49.2 (SD: 17.5), and 63.6% were females. Schizophrenia was the most frequent comorbidity found in 47.6%, followed by bipolar disorder (17.8%), major depressive disorder (10.3%), and obsessive–compulsive disorder (3.7%). Five cases were idiopathic. The most common medications associated with RS were haloperidol (17%), risperidone (14%), aripiprazole (7%), trifluoperazine (5%), and sulpiride (5%). The mean duration of pharmacotherapy before RS was 21.4 weeks (SD: 20.6). RS occurred in association with drug-induced parkinsonism (DIP) in 27.4% and with tardive dyskinesia (TD) in 8.2% of cases. Antipsychotic modification and/or anticholinergic drugs resulted in full or partial recovery in nearly all reported cases in which they were prescribed. Conclusions: RS occurs as a distinct drug-induced syndrome associated primarily but not exclusively with antipsychotics. Distinguishing RS from TD is important because the treatment options for the two disorders are quite different. By contrast, RS may be part of a spectrum of symptoms of DIP with similar course, treatment outcomes, and pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Levodopa‐induced dyskinesias (LID) are frequent in Parkinson's disease (PD). Objective: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). Patients and Methods: PD patients from the 5‐year follow‐up COPPADIS cohort were included. LID were defined as a non‐zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale—part IV (UPDRS‐IV). The UPDRS‐IV was applied at baseline (V0) and annually for 5 years. The 39‐item Parkinson's disease Questionnaire Summary Index (PQ‐39SI) was used to asses QoL. Results: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5‐year follow‐up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (β = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (β = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ‐39SI. Conclusion: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL. [ABSTRACT FROM AUTHOR]

Background: Scapular dyskinesia (SD) is a common condition that affects racquet athletes, impacting their performance and predisposing them to injuries. Objectives: This study aimed to compare joint position sense (JPS) and force reproduction in racquet athletes with and without SD. Methods: This study was conducted as a cross-sectional study. The statistical population consisted of female student-athletes aged 18 to 30 who were engaged in badminton, tennis, and ping pong in Quchan city, both with and without shoulder dyskinesia. The sample included thirty athletes with shoulder dyskinesia and thirty without it, who were randomly selected. Joint Position Sense was assessed at 45 and 135 degrees of abduction. The tools employed in this research encompassed a consent form, an inclinometer (goniometer), the Kibler test, force-reproduction testing, and the McClure test. Data analysis was performed using the Shapiro-Wilk test and an independent t-test in SPSS version 23, with a significance level set at P < 0.05. Results: The results revealed a statistically significant difference in JPS of the shoulder joint between athletes with and without SD at angles of 45 and 135 degrees (P < 0.05). Similarly, the independent t-test analysis demonstrated a significant difference in force reproduction of the shoulder joint between athletes with and without dyskinesis (P < 0.05). Conclusions: These findings underscore the importance of addressing SD and its associated sensory impairments in racquet athletes to optimize performance and reduce the risk of injuries. [ABSTRACT FROM AUTHOR]

L-DOPA-induced dyskinesia (LID) is a debilitating motor side effect arising from chronic dopamine (DA) replacement therapy with L-DOPA for the treatment of Parkinson’s disease. LID is associated with supersensitivity of striatal dopaminergic signaling and fluctuations in synaptic DA following each L-DOPA dose, shrinking the therapeutic window. The heterogeneous composition of the striatum, including subpopulations of medium spiny output neurons (MSNs), interneurons, and supporting cells, complicates the identification of cell(s) underlying LID. We used single-nucleus RNA sequencing (snRNA-seq) to establish a comprehensive striatal transcriptional profile during LID development. Male hemiparkinsonian mice were treated with vehicle or L-DOPA for 1, 5, or 10 d, and striatal nuclei were processed for snRNA-seq. Analyses indicated a limited population of DA D1 receptor–expressing MSNs (D1-MSNs) formed three subclusters in response to L-DOPA treatment and expressed cellular markers of activation. These activated D1-MSNs display similar transcriptional changes previously associated with LID; however, their prevalence and transcriptional behavior were differentially influenced by L-DOPA experience. Differentially expressed genes indicated acute upregulation of plasticity-related transcription factors and mitogen-activated protein kinase signaling, while repeated L-DOPA-induced synaptic remodeling, learning and memory, and transforming growth factor-β (TGF-β) signaling genes. Notably, repeated L-DOPA sensitized Inhba, an activin subunit of the TGF-β superfamily, in activated D1-MSNs, and its pharmacological inhibition impaired LID development, suggesting that activin signaling may play an essential role in LID. These data suggest distinct subsets of D1-MSNs become differentially L-DOPA-responsive due to aberrant induction of molecular mechanisms necessary for neuronal entrainment, similar to processes underlying hippocampal learning and memory [ABSTRACT FROM AUTHOR]

ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7–25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2–34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures. [ABSTRACT FROM AUTHOR]

Background: Childhood gratification syndrome (CGS) refers to self-stimulatory or masturbatory behaviors in children, which may have an onset as early as in infancy (IGS). Aim: The aim of this review is to understand the various clinical manifestations of CGS/IGS and their clinical differentiation from commonly misdiagnosed neurological and physical illnesses and to formulate a preliminary approach to their diagnosis and management. Methods: This narrative review is based on a search of literature over the past 50 years (1972--2022) in three online databases (PubMed/Medline, Embase, and Google Scholar). Results: The behaviors are episodic, occurring for brief periods, involving posturing, stereotypical limb movements, pubic pressure with autonomic hyperactivity, and postepisodic lethargy. They mimic seizures, movement disorders, abdominal pain, and tics. The paper also highlights the gap in the current knowledge to guide future research in the area. CGS usually represents nonpathological "pleasure-seeking" habits of childhood, but at times, it may become problematic for the child and his family. A careful history and videotape analysis of the events confirms the diagnosis and behavioral therapy with parental reassurance as the mainstay of treatment. Conclusion: A better understanding and clinical awareness of the CGS are necessary to prevent misdiagnosis and delay in appropriate intervention. [ABSTRACT FROM AUTHOR]

Background & Objective: This study aimed to investigate the relationship between the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), the Eating and Drinking Ability Classification System (EDACS), the Communication Function Classification System (CFCS), dyskinetic movements and participation levels in children with dyskinetic cerebral palsy (DCP) to attain a comprehensive functional profile of DCP. Methods: Forty children with DCP aged between 5-18 years were included. Functional classification systems: GMFCS, MACS, CFCS, EDACS levels investigated. The Dyskinesia Impairment Scale (DIS) was used for evaluate dyskinetic movements: dystonia and choreoathetosis. Assessment of Life-Habits-Questionnaire (LIFE-H) was used for evaluate participation. Spearman's correlation test was used to evaluate the relationship among functional classification levels, DIS subscales and LIFE-H subdomains. Multivariate simple linear regression, backward model was used to explain relations between LIFE-H subdomains, DIS subscales, GMFCS, MACS, EDACS and CFCS. Results: The mean age was 12.88±4.57 years. Correlations were found between GMFCS-MACS, GMFCS-EDACS, MACS-EDACS, CFCS-MACS, GMFCS-CFCS and EDACS-CFCS (p<0.05); between GMFCS and dystonia upper extremity, dystonia lower extremity total score, dystonia total score (p<0.05); between MACS and dystonia upper extremity, dystonia lower extremity total score, dystonia total score, and dystonia mouth total score (p<0.05). LIFE-H Social-Roles Total Score, Daily-Living-Activities Total Score, LIFE-H-Total-Score were correlated with GMFCS, MACS, EDACS and CFCS (p<0.05). The results of regression analysis showed GMFCS and MACS levels are strong predictors of participations (p<0.05). Conclusions: To plan participatory intervention programs, it is important to understand the levels of participation and differences among children with DCP subtypes according to the ICF framework. [ABSTRACT FROM AUTHOR]

As a neurologist who has followed up countless Parkinson's patients over the last 32 years of my fifty-year career; I denied diagnosing myself with Parkinson's disease (PD), although the seldom mild involuntary "twitches" that occurred in the thumb of my right hand over a two-year period, resembled Parkinson's disease tremor. However, when these involuntary contractions became persistent; considering its similarity to characteristic resting tremor in typical PD, the positive effect of dopaminergic medications, the development of levodopa-induced dyskinesias and other non-motor symptoms, it was clear that the PD diagnosis was accurate. This situation naturally caused me anxiety, and for a year and a half, I kept my diagnosis hidden from everyone except a few close relatives. However, with the encouragement of a psychiatrist friend, when I was able to share my condition with my loved ones, I felt a relative reduction in the burden I was carrying and consequently experienced emotional relief. I am still able to carry out my daily activities independently with a rather low dose of medication, and my PD symptoms do not attract noticeable attention. [ABSTRACT FROM AUTHOR]

Background: Motor complications are well recognized in Parkinson's disease (PD), but their reported prevalence varies and functional impact has not been well studied. Objectives: To quantify the presence, severity, impact and associated factors for motor complications in PD. Methods: Analysis of three large prospective cohort studies of recent‐onset PD patients followed for up to 12 years. The MDS‐UPDRS part 4 assessed motor complications and multivariable logistic regression tested for associations. Genetic risk score (GRS) for Parkinson's was calculated from 79 single nucleotide polymorphisms. Results: 3343 cases were included (64.7% male). Off periods affected 35.0% (95% CI 33.0, 37.0) at 4–6 years and 59.0% (55.6, 62.3) at 8–10 years. Dyskinesia affected 18.5% (95% CI 16.9, 20.2) at 4–6 years and 42.1% (38.7, 45.5) at 8–10 years. Dystonia affected 13.4% (12.1, 14.9) at 4–6 years and 22.8% (20.1, 25.9) at 8–10 years. Off periods consistently caused greater functional impact than dyskinesia. Motor complications were more common among those with higher drug doses, younger age at diagnosis, female gender, and greater dopaminergic responsiveness (in challenge tests), with associations emerging 2–4 years post‐diagnosis. Higher Parkinson's GRS was associated with early dyskinesia (0.026 ≤ P ≤ 0.050 from 2 to 6 years). Conclusions: Off periods are more common and cause greater functional impairment than dyskinesia. We confirm previously reported associations between motor complications with several demographic and medication factors. Greater dopaminergic responsiveness and a higher genetic risk score are two novel and significant independent risk factors for the development of motor complications. [ABSTRACT FROM AUTHOR]

Dyskinesia affects the limbs, trunk, and head and is more prevalent in people with Parkinson’s disease (PD) and a history of falls. More evidence about the effects of dyskinesia on postural control, balance, gait, and fall risk could help improve the quality of life of individuals with PD. This review aims to examine associations between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Such information could lead to new approaches to quality of life improvement among individuals with PD. PubMed, CINAHL, PsycInfo, Scopus, and SciELO will be searched for longitudinal, cohort, and case-control studies published in English or Portuguese in any year that investigated the association between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Two reviewers will independently evaluate the titles, abstracts, and full texts according to PRISMA guidelines to select eligible studies for the review. Data on participants, dyskinesia, postural control, balance, gait, and fall risk will be extracted and summarized in tables. Two reviewers will independently assess the methodological quality of each study using the Newcastle Ottawa quality assessment scale. Meta-analysis will not be performed. The results of this systematic review will offer insight into the effects of dyskinesia on postural control, balance, gait, and fall risk. Such information could significantly contribute to informed decisions about early motor intervention in individuals with PD.

OBJECTIVE: To assess the effect of bilateral subthalamic nucleus deep brain stimulation (B/L STN DBS) on the progression of dyskinesia and the levodopa equivalent daily dose (LEDD) in advanced Parkinson’s disease (APD) patients 6 months postoperatively. METHODS: Seventeen APD patients aged 21–80 years with the minimum modified Hoen & Yahr score of 2 while off medication and poor motor function underwent B/L STN DBS from January 2021 to December 2021. They were assessed preoperatively and 6 months postoperatively using the Unified dyskinesia rating scale (UDysRS) and Unified Parkinson’s Disease Rating Scale Part IV (UPDRS IV) for dyskinesia and LEDD dosage. RESULTS: Significant improvement was observed postoperatively in both UDysRS (pre-op 66.53 ± 24.59, post-op 30.88 ± 12.01; P = 0.000) and UPDRS IV (pre-op 9.24 ± 1.75, post-op 5.76 ± 1.39; P = 0.000) scores. The overall clinical improvement using UDysRS was 52.23 ± 16.23%. Each subscale of UDysRS showed significant improvement postoperatively: ON dyskinesia (pre-op 21 ± 7.7, post-op 13.76 ± 5.79; P < 0.05); OFF dystonia (pre-op 8.53 ± 3.26, post-op 4.94 ± 2.70; P < 0.05); impairment (face, pre-op 2.47 ± 2.52, post-op 0.29 ± 0.98, P < 0.05; neck and trunk, pre-op 6.29 ± 4.55, post-op 0.59 ± 0.87, P < 0.05; arms, pre-op 13.06 ± 5.86, post-op 5.76 ± 3.7, P < 0.05; and legs, pre-op 7.18 ± 5.12, post-op 1.29 ± 1.57, P < 0.05); and disability (pre-op 8 ± 3.46, post-op 4.24 ± 2.25; P < 0.05), suggesting high clinical significance. LEDD (pre-op 673.41 ± 212.69 mg, post-op 386.82 ± 133.01 mg; P = 0.000) showed significant reduction in dosage 6 months postoperatively. LEDD reduction and dyskinesia improvement showed mild-to-moderate positive correlation (r = 0.404). CONCLUSION: B/L STN DBS helps in improving dyskinesia by reducing LEDD in APD patients.

Abstract Background Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. Methods We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT–qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice’s energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. Results Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. Conclusions Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection. Graphical Abstract

Fang-Fang Lin,1 Wei-Yuan Yang,1 Jun-Xiang Zhou,1 Luo-Yuan Cao,2 Ling-Ling Huang1 1Department of Rehabilitation, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, 352000, People’s Republic of China; 2Department of Central Laboratory, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, 352000, People’s Republic of ChinaCorrespondence: Jun-Xiang Zhou; Wei-Yuan Yang, Department of Rehabilitation, Ningde Municipal Hospital Affiliated to Ningde Normal University, No. 7 of Jiaocheng North Road, Jiaocheng District, Ningde, 352000, People’s Republic of China, Tel +86-15159370026 ; +86-13004929861, Email zhoujunxiangz@126.com; weiyuanyang9@126.comObjective: We investigated the clinical characteristics, fall outcomes, and related factors of falls in patients who were hospitalized in the rehabilitation department, and explored strategies to reduce the incidence of falls and prevent falls in patients.Methods: Data from 60 patients who fell in the rehabilitation department between 2016 and 2021 were analyzed for clinical characteristics, associated factors, incidence of falls, injuries, and patient demographics. Under the random stratified sampling method, 60 patients who did not fall during the same period were selected as the control group, and relevant data was collected. Measurement data were compared using an independent sample t-test. Enumeration data were compared using chi-squared (χ2) test was employed to compare these data between the two groups. Non-parametric data were analyzed using the Mann–Whitney U-test. Factors potentially influencing falls were scrutinized through both univariate and binary logistic regression analyses.Results: The median annual incidence of falls among patients who were hospitalized in the rehabilitation department was 0.04%, while the overall fall injury rate was 60%. Falls were most prevalent within 30 days of hospitalization (71.67%). The most common fall-related condition was craniocerebral disease (83.33%). The incidents of falls location of fall were mainly reported in nearby areas of rehabilitation ward (70%). Most accidents occurred between 7:00 a.m.– 12:00 p.m. and 3:01 p.m.– 6:00 p.m. (63.33%), and dyskinesia was the most common cause of falls (71.67%). There were 39 patients (65.00%) with Barthel Index (BI) scores ranging between 40– 60.Conclusion: Patients in the rehabilitation department had a greater incidence of falls and fall injuries. Within 30 days of admission, patients with moderately dependent craniocerebral disorders and dyskinesia frequently experienced falls during typical daytime shifts in areas characterized by endemic conditions.Keywords: daily living activities, dyskinesia, fall, hospitalized patients, rehabilitation department, retrospective analysis

Introduction: The association between the visceral swallowing pattern (VSP) and dentofacial abnormalities remains controversial. This cross-sectional study aimed to investigate the association between the VSP and various factors including type of birth, gender, tongue posture, lip incompetence, eruption of primary molars, habits and the presence of malocclusions in children with primary and early mixed dentition. Material and method: A total of 219 children (102 boys and 117 girls) were evaluated using a combination of a questionnaire and a structured clinical examination by one pediatric specialist dentist. Kittel’s method of tongue posture evaluation and the Payne technique for assessment of swallowing pattern were included in the clinical examination of myofunctional status. After checking for normality, normal and non-normal distributed data were analyzed using two-sample t-test and Mann-Whitney U test, respectively. Analysis of categorical variables was done using a chi-square test, and Bonferroni correction was used as correction for multiple comparisons. Results: A total of 56.2 % of the study population had a VSP. The chi-square test indicated a statistically significant higher presence of VSP in male gender. Statistically significant associations were seen between the VSP and lip incompetency, pathologic resting tongue position, habits, anterior open bite and increased overjet. On the other hand, no statistically significant associations were found between VSP and children’s age within the sample population, type of birth, uni- or bilateral crossbites, increased overbite, edge-to-edge anterior bite or completion of eruption of primary molars and/or permanent incisors. Conclusions: The association between VSP and male gender, pathologic tongue posture, lip incompetency and habits and occlusal traits such as anterior open bite and increased anterior overjet is supported by the results of the present study.

Abstract Objectives Overactive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson’s disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD. Methods 1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia. Results This study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p 5) (p 5. Discussion This study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies.

L-3,4-dihydroxyphenylalanine (L-DOPA) is the main treatment for Parkinson's disease (PD) but with long term administration, motor complications such as dyskinesia are induced. Glycine transporter 1 (GlyT1) inhibition was shown to produce an anti-dyskinetic effect in parkinsonian rats and primates, coupled with an improvement in the anti-parkinsonian action of L-DOPA. The expression of GlyT1 in the brain in the dyskinetic state remains to be investigated. Here, we quantified the levels of GlyT1 across different brain regions using [3H]-NFPS in the presence of Org-25,935. Brain sections were chosen from sham-lesioned rats, L-DOPA-naïve 6-hydroxydopamine (6-OHDA)-lesioned rats and 6-OHDA-lesioned rats exhibiting mild or severe abnormal involuntary movements (AIMs). [3H]-NFPS binding decreased in the ipsilateral and contralateral thalamus, by 28% and 41%, in 6-OHDA-lesioned rats with severe AIMs compared to sham-lesioned animals (P < 0.01 and 0.001). [3H]-NFPS binding increased by 21% in the ipsilateral substantia nigra of 6-OHDA-lesioned rats with severe AIMs compared to 6-OHDA-lesioned rats with mild AIMs (P < 0.05). [3H]-NFPS binding was lower by 19% in the contralateral primary motor cortex and by 20% in the contralateral subthalamic nucleus of 6-OHDA-lesioned rats with mild AIMs animals compared to rats with severe AIMs (both P < 0.05). The severity of AIMs scores positively correlated with [3H]-NFPS binding in the ipsilateral substantia nigra (P < 0.05), ipsilateral entopeduncular nucleus (P < 0.05) and contralateral primary motor cortex (P < 0.05). These data provide an anatomical basis to explain the efficacy of GlyT1 inhibitors in dyskinesia in PD. [ABSTRACT FROM AUTHOR]

Motor and cognitive alterations in schizophrenia-spectrum disorders (SSD) share common neural underpinnings, highlighting the necessity for a thorough exploration of the connections between these areas. This relationship is crucial, as it holds potential significance in unraveling the underlying mechanisms of SSD pathophysiology, ultimately leading to advancements in clinical staging and treatment strategies. The purpose of this review was to characterize the relationship between different hyper and hypokinetic domains of motor alterations and cognition in SSD. We systematically searched the literature (PROSPERO protocol CRD42019145964) and selected 66 original scientific contributions for review, published between 1987 and 2022. A narrative synthesis of the results was conducted. Hyper and hypokinetic motor alterations showed weak to moderate negative correlations with cognitive function across different SSD stages, including before antipsychotic treatment. The literature to date shows a diverse set of methodologies and composite cognitive scores hampering a strong conclusion about which specific cognitive domains were more linked to each group of motor alterations. However, executive functions seemed the domain more consistently associated with parkinsonism with the results regarding dyskinesia being less clear. Akathisia and catatonia were scarcely discussed in the reviewed literature. The present review reinforces the intimate relationship between specific motor alterations and cognition. Identified gaps in the literature challenge the formulation of definitive conclusions. Nevertheless, a discussion of putative underlying mechanisms is included, prompting guidance for future research endeavors. [ABSTRACT FROM AUTHOR]

Respiratory distress in the newborn is associated with numerous etiologies, some common and some rare. When respiratory distress is accompanied by laterality defects, namely, situs inversus (SI), the index of suspicion for comorbid primary ciliary dyskinesia (PCD) should be raised. Primary ciliary dyskinesia is characterized by ciliary dysmotility and the accumulation of thick secretions in the airways that obstruct air and gas exchange. Neonatal clinicians should know that while PCD is definitively diagnosed in infancy or early childhood, findings suspicious for PCD should be communicated to primary care providers at discharge from the hospital to facilitate timely subspecialty involvement, diagnosis, and treatment. This article will present a case report of a term newborn with SI totalis who was later diagnosed with PCD. We will discuss epidemiology, pathophysiology, clinical manifestations, and diagnostics, followed by management strategies. Additionally, we discuss the outpatient needs and lifespan implications. [ABSTRACT FROM AUTHOR]

Background: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. Methods: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT–qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. Results: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. Conclusions: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection. [ABSTRACT FROM AUTHOR]

Introduction: In the advanced stages of Parkinson's disease (PD), motor complications such as wearing-off and dyskinesia are problematic and vary daily. These symptoms need to be monitored precisely to provide adequate care for patients with advanced PD. Methods: This study used wearable devices to explore biomarkers for motor complications by measuring multiple biomarkers in patients with PD residing in facilities and combining them with lifestyle and clinical assessments. Data on the pulse rate and activity index (metabolic equivalents) were collected from 12 patients over 30 days. Results: The pulse rate and activity index during the off- and on-periods and dyskinesia were analyzed for two participants; the pulse rate and activity index did not show any particular trend in each participant; however, the pulse rate/activity index was significantly greater in the off-state compared to that in the dyskinesia and on-states, and this index in the dyskinesia state was significantly greater than that in the on-state in both participants. Conclusion: These results suggest the pulse rate and activity index combination would be a useful indicator of wearing-off and dyskinesia and that biometric information from wearable devices may function as a digital diary. Accumulating more cases and collecting additional data are necessary to verify our findings. [ABSTRACT FROM AUTHOR]

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies. [ABSTRACT FROM AUTHOR]

An seven-month-old female Sichuan golden snub-nosed monkey (Rhinopithe⁃cus roxellana) at a zoo in Nanjing suddenly presented clinical symptoms such as asymmetric motor dysfunction, difficulty in climbing, atrophy and weakness of limb muscles, and no pain response in toes. The case was diagnosed as polyneuritis by means of electron computed tomography (ECT), nuclear magnetic resonance (NMR), viral testing and trace element testing, combined with the clinical manifestations of the affected animal. Through more than five months of combined treatment with methylcobalamin and nerve growth factor as well as massage therapy methods, clinical observations revealed that the animal’s hindlimb muscle group strength was restored and was able to crawl on its own. The results suggest that a synergistic treatment regimen of methylcobalamin combined with nerve growth factor therapy and massage methods is effective in polyneuritis in Sich⁃uan golden snub-nosed monkeys. [ABSTRACT FROM AUTHOR]

The association between the visceral swallowing pattern (VSP) and dentofacial abnormalities remains controversial. This cross-sectional study aimed to investigate the association between the VSP and various factors including type of birth, gender, tongue posture, lip incompetence, eruption of primary molars, habits and the presence of malocclusions in children with primary and early mixed dentition. A total of 219 children (102 boys and 117 girls) were evaluated using a combination of a questionnaire and a structured clinical examination by one pediatric specialist dentist. Kittel's method of tongue posture evaluation and the Payne technique for assessment of swallowing pattern were included in the clinical examination of myofunctional status. After checking for normality, normal and non-normal distributed data were analyzed using two-sample t -test and Mann-Whitney U test, respectively. Analysis of categorical variables was done using a chi-square test, and Bonferroni correction was used as correction for multiple comparisons. A total of 56.2 % of the study population had a VSP. The chi-square test indicated a statistically significant higher presence of VSP in male gender. Statistically significant associations were seen between the VSP and lip incompetency, pathologic resting tongue position, habits, anterior open bite and increased overjet. On the other hand, no statistically significant associations were found between VSP and children's age within the sample population, type of birth, uni- or bilateral crossbites, increased overbite, edge-to-edge anterior bite or completion of eruption of primary molars and/or permanent incisors. The association between VSP and male gender, pathologic tongue posture, lip incompetency and habits and occlusal traits such as anterior open bite and increased anterior overjet is supported by the results of the present study. [ABSTRACT FROM AUTHOR]

Belly dancer's dyskinesia (BDD) is characterized by involuntary abdominal wall movements that are rhythmic, repetitive, and dyskinetic. The present study aims to review BDD's etiology, pathophysiology, and management. We searched six databases to locate existing reports on BDD published from 1990 to October 2023 in electronic form. A total of 47 articles containing 59 cases were found. The majority of the patients affected by BDD were female, accounting for 61.01% (36/59) of the cases. The mean and median ages were 49.8 (standard deviation: 21.85) and 52 years (range: 7-85), respectively. The BDD was unilateral in only 3.38% (2/59). The most commonly reported causes associated with BDD were 17 idiopathic, 11 drug-induced, 11 postsurgical procedures, 5 pregnancies, and 4 Vitamin B12 deficiencies. BDD is a diagnosis of exclusion, and other more common pathologies with similar presentation should be ruled out initially. Differential diagnostic reasoning should include diaphragmatic myoclonus, cardiac conditions, truncal dystonia, abdominal motor seizures, propriospinal myoclonus, and functional or psychiatric disorders. [ABSTRACT FROM AUTHOR]

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 1 mg/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 1 mg/kg to L‐DOPA diminished peak dose dyskinesia by 47% (P < 0.05) and 69% (P < 0.001). Nelotanserin 0.3 and 1 mg/kg also reduced the severity of global dyskinesia, by 40% (P < 0.01) and 55% (P < 0.001), when compared to vehicle. Nelotanserin 0.1 mg/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. [ABSTRACT FROM AUTHOR]

Objectives: Overactive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson's disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD. Methods: 1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia. Results: This study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p < 0.001), H-Y scores (p < 0.001), NMSQ (p < 0.001) and MoCA scores (p < 0.001), and lower MMSE scores (p < 0.001) are identified. The multivariate logistic regression confirms that disease duration (p = 0.041), LEDD (p < 0.001), UPDRSII (p < 0.001), MoCA (p = 0.024), urgency (p < 0.001), frequency (p < 0.001), and nocturia (p = 0.002) are independent risk factors for dyskinesia. Trend analysis indicates that the risk of dyskinesia significantly increases when patients exhibit moderate to severe OAB symptoms (OABSS > 5) (p < 0.001). No significant interactions were found between OABSS and age, gender, disease duration, LEDD, and NMSQ scores in different subgroups, indicating that dyskinesia is more pronounced in patients with OABSS > 5. Discussion: This study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests that co‐administration of the 5‐HT1A agonist buspirone and the 5‐HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Objectives: Assess the therapeutic potential of a fixed‐dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa‐induced dyskinesia. Methods: Single‐center, randomized, placebo‐controlled, two‐way crossover study (NCT02439203) of a fixed‐dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak‐effect dyskinesia. Results: Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: −4.2 [−6.1, −2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [−0.1, 1.3]). No serious adverse events were reported. Conclusions: In this proof‐of‐concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. Continuous DBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and globus pallidus (dual target DBS) in a prospective within-participant, clinical trial in six patients with Parkinson's disease (n = 6, 55–65 years, n = 2 females). Dual target cDBS was tested for Parkinson's disease symptom control annually over 2 years, measured by motor rating scales, on time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral aDBS using a novel distributed (off-implant) architecture. In the home setting, we collected tremor and dyskinesia scores as well as individualized β and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by Unified Parkinson's Disease Rating Scale (UPDRS) to a greater degree than either region alone (P < 0.05, linear mixed model) in the cohort. The amplitude of β-oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (P < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artefacts and demonstrated a correlation between STN β amplitude and DBS amplitude. Proportional plus integral control of aDBS reduced average power, while preserving UPDRS III scores in the clinic (P = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n = 3 , P > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of Parkinson's disease over DBS of either the STN or globus pallidus alone. When combined with proportional plus integral aDBS, stimulation power may be reduced, while preserving the increased benefit of dual target DBS. [ABSTRACT FROM AUTHOR]

Introduction. ADCY5-related dyskinesia is a rare neurological disease caused by mutations in the gene encoding the adenylyl cyclase 5 (ADCY5) isoform, a protein that plays an important role in intracellular transmission. Variants in ADCY5 are associated with a spectrum of neurological disease encompassing dyskinesia, chorea, and dystonia. State of the-art. ADCY5 mutations result in clinically heterogeneous manifestations which comprise a range of core and less to highly variable symptoms. Due to the heterogeneous nature and difficulty in diagnosis of the disorder, available treatments are highly limited. Clinical implications. ADCY5-related dyskinesia was reported in 52 individuals in the literature over a five-year period (January 2017 to January 2022). We have listed all the symptoms and their frequency. The most common symptom reported in these patients was dystonia. Over 50% of patients developed dyskinesia and chorea. We report two cases of familial occurrence of symptomatic ADCY5-related dyskinesia. A 45-year-old patient presented with involuntary movements which had been occurring since childhood. The proband's neurological examination revealed dysarthria, involuntary myoclonic twitches, and choreic movements. The patient's 9-year-old son had developed involuntary movements, mainly chorea and dystonia. Future directions. This paper aims to summarise the recent literature on ADCY5-related neurological disorders and to present a new case of a Polish family with ADCY5 mutation. Genetic diagnostics are important in the context of possible future targeted treatments. [ABSTRACT FROM AUTHOR]

Parkinson's disease is caused by a selective vulnerability and cell loss of dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal dopamine depletion. In Parkinson's disease therapy, dopamine loss is counteracted by the administration of L-DOPA, which is initially effective in ameliorating motor symptoms, but over time leads to a burdening side effect of uncontrollable jerky movements, termed L-DOPA-induced dyskinesia. To date, no efficient treatment for dyskinesia exists. The dopaminergic and serotonergic systems are intrinsically linked, and in recent years, a role has been established for pre-synaptic 5-HT1a/b receptors in L-DOPA-induced dyskinesia. We hypothesized that post-synaptic serotonin receptors may have a role and investigated the effect of modulation of 5-HT4 receptor on motor symptoms and L-DOPA-induced dyskinesia in the unilateral 6-OHDA mouse model of Parkinson's disease. Administration of RS 67333, a 5-HT4 receptor partial agonist, reduces L-DOPA-induced dyskinesia without altering L-DOPA's pro-kinetic effect. In the dorsolateral striatum, we find 5-HT4 receptor to be predominantly expressed in D2R-containing medium spiny neurons, and its expression is altered by dopamine depletion and L-DOPA treatment. We further show that 5-HT4 receptor agonism not only reduces L-DOPA-induced dyskinesia, but also enhances the activation of the cAMP-PKA pathway in striatopallidal medium spiny neurons. Taken together, our findings suggest that agonism of the post-synaptic serotonin receptor 5-HT4 may be a novel therapeutic approach to reduce L-DOPA-induced dyskinesia.

Key Clinical Message Belly dancer dyskinesia, a rare disease, may often be overlooked as a regular nonspecific abdominal pain, and therefore, high index of clinical suspicion is required to avert misdiagnosis.

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AbstractContext Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson’s disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD.Objective To explore the synergistic effect of NJ combined with levodopa against PD.Materials and methods The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways.Results Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p

Chorea-acanthocytosis is a rare neurological disorder that produces involuntary body movements, along with a condition of misshapen red blood cells that is characterized by appearing in early adulthood. There are numerous orofacial manifestations linked to chorea-acanthocytosis that the dental practitioner must consider in early and late stages of the disease, such as chronic oral ulcerations, chronic mouth grinding, difficulty swallowing, and biting the lip and tongue, among others. This case, the first to the authors' knowledge to address the area of orofacial pain, provides general signs and symptoms of the disorder and management following a multidisciplinary approach. The life span of patients with this disorder is generally shortened, and correct management is essential to improve the quality of life. [ABSTRACT FROM AUTHOR]

Alterations of serotonin type 4 receptor levels are linked to mood disorders and cognitive deficits in several conditions. However, few studies have investigated 5-HT4R alterations in movement disorders. We wondered whether striatal 5-HT4R expression is altered in experimental parkinsonism. We used a brain bank tissue from a rat and a macaque model of Parkinson's disease (PD). We then investigated its in vivo PET imaging regulation in a cohort of macaques. Dopaminergic depletion increases striatal 5-HT4R in the two models, further augmented after dyskinesia-inducing L-Dopa. Pending confirmation in PD patients, the 5-HT4R might offer a therapeutic target for dampening PD's symptoms. [ABSTRACT FROM AUTHOR]

Studies have reported positive associations between drug-induced movement disorders (DIMDs) and symptoms of psychosis in patients with schizophrenia. However, it is not clear which subtypes of symptoms are related to each other, and whether one symptom precedes another. The current report assessed both concurrent and temporal associations between DIMDs and symptoms of psychosis in a community-based sample of homeless individuals. Participants were recruited in Vancouver, Canada. Severity of DIMDs and psychosis was rated annually, allowing for the analysis of concurrent associations between DIMDs and Positive and Negative Syndrome Scale (PANSS) five factors. A brief version of the PANSS was rated monthly using five psychotic symptoms, allowing for the analysis of their temporal associations with DIMDs. Mixed-effects linear and logistic regression models were used to assess the associations. 401 participants were included, mean age of 40.7 years (SD = 11.2) and 77.4% male. DIMDs and symptoms of psychosis were differentially associated with each other, in which the presence of parkinsonism was associated with greater negative symptoms, dyskinesia with disorganized symptoms, and akathisia with excited symptoms. The presence of DIMDs of any type was not associated with depressive symptoms. Regarding temporal associations, preceding delusions and unusual thought content were associated with parkinsonism, whereas dyskinesia was associated with subsequent conceptual disorganization. The current study found significant associations between DIMDs and symptoms of psychosis in individuals living in precarious housing or homelessness. Moreover, there were temporal associations between parkinsonism and psychotic symptoms (delusions or unusual thought content), and the presence of dyskinesia was temporally associated with higher odds of clinically relevant conceptual disorganization. [ABSTRACT FROM AUTHOR]