Management of tardive dyskinesia and tardive dystonia with clozapine: A retrospective study.

AIM: This retrospective study aimed to evaluate the long-term effectiveness of switching to clozapine in the management of tardive syndromes (TS). METHODOLOGY: The treatment records of patients who had TS at the time of starting clozapine, were reviewed and demographic and clinical data was extracted on a predesigned performa. RESULTS: About three-fourth (74.2 %) of the study subjects had tardive dystonias and two-third (69.7 %) had tardive dyskinesia at the time of starting clozapine. About half (48.5 %) of the patients had both tardive dystonia and dyskinesia. A small proportion (13.6 %) also had tardive akathisia at the time of starting clozapine. About three-fourth (72.2 %) of the patients had >50 % reduction, and about two-third (66.6 %) of the patients had >75 % reduction and nearly half (54.5 %) of the patients had complete resolution of dyskinesia at the last follow-up. Similar trends were seen in reduction in dystonia, i.e., >50 % reduction in 74.3 %, >75 % reduction in 62.2 % and complete resolution was seen in 56.1 %. CONCLUSIONS: The present study suggest that clozapine is useful in the management of drug induced tardive dyskinesia and tardive dystonia.

Case report: Case analysis of multiple sclerosis with preclinical systemic lupus erythematosus presenting as rare bilateral horizontal gaze palsy.

We present an analysis of a case initially manifesting as bilateral horizontal gaze palsy, eventually diagnosed as multiple sclerosis (MS) with preclinical systemic lupus erythematosus (p-SLE). The patient, a 25-year-old male, exhibited restricted movement in both eyes. Cranial MRI revealed multiple demyelinating lesions; serum analyses indicated elevated levels of antinuclear antibodies (ANA), anti-Sm antibodies, and anti-nRNP antibodies. Oligoclonal bands were identified in the cerebrospinal fluid. Neurophysiological assessments demonstrated damage to the optic, auditory, and facial nerves. Given the clinical presentation, laboratory findings, and the progression of the disease, the final diagnosis was confirmed as MS associated with p-SLE. The onset of MS with oculomotor disturbances is rare and may be easily confused with neuropsychiatric systemic lupus erythematosus (NPSLE). Furthermore, the differentiation of p-SLE from undifferentiated connective tissue disease (UCTD) in the early stages presents significant challenges. Early identification of risk factors and close monitoring of disease activity is crucial for an accurate diagnosis.

Effects of Using a Special Weighted Vest on Muscle Activity around the Scapula during Knee Push-Up Plus in Healthy Subjects.

Muscle imbalances in the upper body can lead to ineffective movement patterns and potential injury. The purpose of this study was to investigate the muscle activity, impact, and muscle activation ratio of the serratus anterior (SA), upper trapezius (UT), lower trapezius (LT), and pectoralis major (PM) during the knee push-up plus (KPUP) exercise under various loads. METHOD: Electromyography assessed scapular muscle activity in 32 healthy adults (15 males, 17 females) during three KPUP variations. RESULTS: PM and UT showed no significant activity differences across loads, whereas SA and LT did. SA activity was significantly higher in the weighted KPUP (WKPUP) 3 kg than that in KPUP and WKPUP 1 kg. LT activity was also significantly higher in WKPUP 3 kg compared to KPUP and WKPUP 1 kg, with KPUP showing higher activity than WKPUP 1 kg. PM/SA ratios remained consistent across loads, while UT/LT ratios varied significantly, being notably lower at 3 kg compared to 0 kg and 1 kg. Similarly, UT/SA ratios differed significantly among loads, being notably lower at 3 kg and 1 kg compared to 0 kg. CONCLUSION: WKPUP with 3 kg demonstrated significantly higher SA and LT activity compared to KPUP and WKPUP 1 kg. The lowest UT/LT ratio was observed during the WKPUP 3 kg, suggesting its effectiveness for optimizing muscle activation balance during KPUP exercises. These findings may inform the development of exercise protocols aimed at improving scapular stabilization.

Airway Clearance Techniques in Primary Ciliary Dyskinesia: A Systematic Review.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a respiratory disorder that impairs mucociliary clearance, leading to decreased lung function. Conventional chest physiotherapy (CCP) is the traditional airway clearance technique (ACT) and is considered a standard treatment for PCD patients. This systematic review investigated whether device supported ACTs are better alternatives for improving lung function and/or quality of life in PCD, compared with CCP. METHODS: The OVID Medline, PubMed, CINAHL, and Cochrane databases were searched. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to aggregate the data. This systematic review has been registered on the International Prospective Register of Systematic Reviews website. RESULTS: Of the 389 citations that resulted from our literature search, 2 randomized crossover trials that included a total of 54 patients were analyzed. The certainty of the aggregated study evidence was very low. No difference was identified between device-supported ACTs and CCP in terms of forced vital capacity and forced expiratory volume in 1 second in PCD patients aged 6 to 20 years. CONCLUSION: Device-supported ACTs could be considered alternative treatment options to replace CCP. High quality research is required to confirm this result.

Suspected paroxysmal dyskinesia in four small-breed dogs: Clinical presentation, diagnosis, management and prognosis.

This case report details the clinical presentation, diagnosis, management and prognosis of paroxysmal dyskinesia (PD) in four small-breed dogs, each weighing under 6 kg: A 7-year-old spayed female Pomeranian, an 8-year-old female mixed breed, a 1-year-old female Pomeranian and a 9-year-old castrated male Poodle. These dogs were referred to our hospital due to movement disorders. Diagnosis was facilitated by video recordings of the episodes, assessing motor activity, consciousness, episode duration, any pre- or post-episodic behaviour as well as the presence of autonomic signs. Magnetic resonance imaging conducted on two of the dogs returned unremarkable results. Treatment trials included a gluten-free diet for all four dogs, with two also receiving acetazolamide. This intervention led to a decrease in the frequency of abnormal movement in all patients. Our findings suggest that PD in dogs can be effectively diagnosed through detailed symptom description using videos and questionnaires. Furthermore, once diagnosed, a combination of nutritional and medical management can be beneficial.

Inhaled Medications for Maintenance Therapy in Pediatric Noncystic Fibrosis Bronchiectasis.

OBJECTIVE: This review focuses on evaluating literature for the use of inhaled mucolytics (hypertonic saline, mannitol, and dornase alfa), inhaled antibiotics (tobramycin, aztreonam, colistin, and amikacin), and inhaled corticosteroids in pediatric noncystic fibrosis bronchiectasis. DATA SOURCES: A literature search via PubMed was conducted using the search terms "non-cystic fibrosis bronchiectasis," "primary ciliary dyskinesia," and "bronchiectasis" in combination with each inhaled agent of interest. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they were specific to patients with a clinical diagnosis of noncystic fibrosis bronchiectasis published from 1998 to July 2024. DATA SYNTHESIS: Several inhaled medications can be considered as maintenance therapies for pediatric patients with noncystic fibrosis bronchiectasis. Hypertonic saline could be considered for its potential airway clearance benefits and low risk of causing harm. Inhaled antipseudomonal antibiotics should be considered in patients who are colonized with Pseudomonas aeruginosa. Inhaled corticosteroid therapy should be reserved for patients with concomitant asthma. Dornase alfa has shown worse outcomes in adults with noncystic fibrosis bronchiectasis and should be used with caution. Risks and benefits should be carefully considered when evaluating these therapies for use in noncystic fibrosis bronchiectasis, and patient-specific treatment regimens should be developed. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Chronic management of pediatric noncystic fibrosis bronchiectasis remains challenging due to paucity of applicable literature. Risks and benefits of different agents are discussed in this article with recommendations for application to clinical practice based on studies performed in both adult and pediatric patients with noncystic fibrosis bronchiectasis. CONCLUSION: Several inhaled medications could be considered as maintenance therapies for pediatric patients with noncystic fibrosis bronchiectasis, with more robust evidence to support use of inhaled antipseudomonal antibiotics and hypertonic saline compared with other available agents. Further investigation is needed to identify a clear place in therapy for inhaled therapies in pediatric noncystic fibrosis bronchiectasis.

Pain Fluctuations in Parkinson's Disease and Their Association with Motor and Non-Motor Fluctuations.

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.

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.

Evaluation and Management of Biliary Dyskinesia in Children and Adolescents: A Systematic Review From the APSA Outcomes and Evidence-Based Committee.

INTRODUCTION: The diagnosis and management of biliary dyskinesia in children and adolescents remains variable and controversial. The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee (APSA OEBP) performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Through an iterative process, the membership of the APSA OEBP developed five a priori questions focused on diagnostic criteria, indications for cholecystectomy, short and long-term outcomes, predictors of success/benefit, and outcomes of medical management. A systematic review was conducted, and articles were selected for review following Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. Risk of bias was assessed using Methodologic Index for Non-Randomized Studies (MINORS) criteria. The Oxford Levels of Evidence and Grades of Recommendation were utilized. RESULTS: The diagnostic criteria for biliary dyskinesia in children and adolescents are not clearly defined. Cholecystectomy may provide long-term partial or complete relief in some patients; however, there are no reliable predictors of symptom relief. Some patients may experience resolution of symptoms with non-operative management. CONCLUSIONS: Pediatric biliary dyskinesia remains an ill-defined clinical entity. Pediatric-specific guidelines are necessary to better characterize the condition, guide work-up, and provide management recommendations. Prospective studies are necessary to more reliably identify patients who may benefit from cholecystectomy. LEVEL OF EVIDENCE: Level 3-4. TYPE OF STUDY: Systematic Review of Level 3-4 Studies.

Gray matter structural alterations of cortico-striato-thalamo-cortical loop in familial Paroxysmal Kinesigenic Dyskinesia.

Background: Previous studies have indicated that patients with Paroxysmal Kinesigenic Dyskinesia (PKD) exhibit reduced gray matter volume in certain brain regions within the cortico-striato-thalamo-cortical (CSTC) loop. However, a comprehensive investigation specifically targeting the CSTC loop in PKD has never been conducted. Objectives: To provide evidence for the involvement of the CSTC loop in the pathogenesis of PKD from the perspective of structural alterations, this study carried out a surface-based morphometry (SBM), voxel-based morphometry (VBM), and structural covariance networks (SCN) combined analysis in familial PKD patients. Methods: A total of 8 familial PKD patients and 10 healthy family members were included in the study and underwent Brain MRI examinations. Based on 3D T1 MPRAGE data, neuroimaging metrics of cortical thickness from SBM, subcortical nuclei volume from VBM, and covariance coefficient from SCN were used to systematically investigate the brain structural alterations along the CSTC loop of PKD patients. Results: A significant decrease in the average cortical thickness of the left S1 region in the PKD group was observed. The volumes of subcortical nuclei, including the thalamus, putamen, and globus pallidus were reduced, with a pronounced effect observed in the bilateral putamen. And the structural covariance connection between the left putamen and the left globus pallidus was significantly strengthened. Conclusions: The study confirms the involvement of the CSTC loop in the pathogenesis of PKD from the perspective of structural alterations, and the findings may provide potential targets for objective diagnosis and therapeutic monitoring of PKD.

Investigating genotype-phenotype correlations in primary ciliary dyskinesia: a sibling cohort study.

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) is a complex mostly autosomal recessive disorder characterized by dysfunction of primary motor cilia, leading to multisystemic manifestations, primarily affecting the rhino-sinopulmonary system. Despite advancements in understanding its pathogenesis, genotype-phenotype correlations are not fully elucidated. Utilizing sibling cohorts offers a promising approach to investigate these genotype-phenotype correlations in PCD. MATERIALS AND METHODS: This retrospective cohort study, conducted from 2010 to 2023 at Soroka University Medical Center in Be'er-Sheva, Israel, included patients with a confirmed diagnosis of PCD. Variables and outcomes compared include typical presenting symptoms, lung function, structural changes in chest tomography (CT), and anthropometric data. RESULTS: Seventeen sibling patients from eight families met the inclusion criteria. At the last follow-up visit, the median age was 16 years. Genetic diagnosis revealed homozygous pathogenic variants including DNAH11, DNAAF3, DNAL1, and ZMYND10. Full concordance rates were observed for unexplained neonatal respiratory distress, chronic cough, and rhinosinusitis in patients with DNAH11 mutations. The family with the DNAAF3 mutation exhibited the lowest difference in Forced Expiratory Volume in 1 s (FEV1) Z-scores (0.48), but the highest differences in Forced Vital Capacity (FVC) Z-scores (3.39). High differences in FEV1 Z-scores were identified in the family with the DNAL1 mutation (2.06), while the lowest differences in FVC Z-scores (0.39) were observed in the same family. DISCUSSION: High concordance rates for certain mutations in clinical features suggest potential genotype-phenotype correlations, in contrast to weak concordance in lung function. Challenges remain in establishing direct correlations between genetic mutations and clinical outcomes.

Lung ultrasound in children with primary ciliary dyskinesia or cystic fibrosis.

INTRODUCTION: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are respiratory conditions requiring regular chest radiography (CXR) surveillance to monitor pulmonary disease. However, CXR is insensitive for lung disease in CF and PCD. Lung ultrasound (LU) is a radiation-free alternative showing good correlation with severity of lung disease in CF but has not been studied in PCD. METHOD: Standardized, six-zone LU studies and CXR were performed on a convenience sample of children with PCD or CF during a single visit when well. LU studies were graded using the LU scoring system, while CXR studies received a modified Chrispin-Norman score. Scores were correlated with clinical outcomes. RESULT: Data from 30 patients with PCD and 30 with CF (median age PCD 11.5 years, CF 9.1 years) with overall mild pulmonary disease (PCD median FEV1 90% predicted, CF FEV1 100%) were analyzed. LU abnormalities appear in 11/30 (36%) patients with PCD and 9/30 (30%) with CF. Sensitivity, specificity, positive predictive, and negative predictive values for abnormal LU compared to the gold standard of CXR are 42%, 61%, 42%, and 61% in PCD, and 44%, 81%, 50%, and 77% in CF, respectively. Correlation between LU and CXR scores are poor for both diseases (PCD r = -0.1288, p = 0.4977; CF r = 0.0343, p = 0.8571), and LU score does not correlate with clinical outcomes in PCD. CONCLUSION: The correlation of LU findings with CXR surveillance studies is poor in patients with mild disease burdens from PCD or CF, and LU scores do not correlate with clinical outcomes in PCD.

A Systematic Review of Oral Vertical Dyskinesia ("Rabbit" Syndrome).

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.

Pharmacodynamic, pharmacokinetic and rat brain receptor occupancy profile of NLX-112, a highly selective 5-HT1A receptor biased agonist.

NLX-112 (i.e., F13640, befiradol) exhibits nanomolar affinity, exceptional selectivity and full agonist efficacy at serotonin 5-HT1A receptors. NLX-112 shows efficacy in rat, marmoset and macaque models of L-DOPA induced dyskinesia (LID) in Parkinson's disease and has shown clinical efficacy in a Phase 2a proof-of-concept study for this indication. Here we investigated, in rats, its pharmacodynamic, pharmacokinetic (PK) and brain 5-HT1A receptor occupancy profiles, and its PK properties in the absence and presence of L-DOPA. Total and free NLX-112 exposure in plasma, CSF and striatal ECF was dose-proportional over the range tested (0.04, 0.16 and 0.63 mg/kg i.p.). NLX-112 exposure increased rapidly (Tmax 0.25-0.5h) and exhibited approximately threefold longer half-life in brain than in plasma (1.1 and 3.6h, respectively). At a pharmacologically relevant dose of 0.16 mg/kg i.p., previously shown to elicit anti-LID activity in parkinsonian rats, brain concentration of NLX-112 was 51-63 ng/g from 0.15 to 1h. In microPET imaging experiments, NLX-112 showed dose-dependent reduction of 18F-F13640 (i.e., 18F-NLX-112) brain 5-HT1A receptor labeling in cingulate cortex and striatum, regions associated with motor control and mood, with almost complete inhibition of labeling at the dose of 0.63 mg/kg i.p.. Co-administration of L-DOPA (6 mg/kg s.c., a dose used to elicit LID in parkinsonian rats) together with NLX-112 (0.16 mg/kg i.p.) did not modify PK parameters in rat plasma and brain of either NLX-112 or L-DOPA. Here, we demonstrate that NLX-112's profile is compatible with 'druggable' parameters for CNS indications, and the results provide measures of brain concentrations and 5-HT1A receptor binding parameters relevant to the anti-dyskinetic activity of the compound.

Pisa Syndrome Secondary to Drugs: A Scope Review.

BACKGROUND: Pisa syndrome, also known as pleurothotonus, is a neurological condition characterized by more than ten degrees of constant lateral curvature of the spine when upright. In this way, the present manuscript aims to systematically review Pisa syndrome secondary to drugs. METHODS: Two reviewers identified and assessed relevant reports in six databases without language restriction between January 1990 and June 2024. RESULTS: The prevalence of Pisa syndrome varied from 0.037 to 9.3%. We found 109 articles containing 191 cases of drug-induced Pisa syndrome reported in the literature. The mean and median ages were 59.70 (SD = 19.02) and 67 (range = 12-98 years). The most prevalent sex was female, 56.91% (107/188). The most frequent medications associated with Pisa syndrome were acetylcholinesterase inhibitors in 87 individuals. Of 112 individuals in which the onset time from the medication to the movement disorder occurrence was reported, 59 took place within a month. In this way, a return to baseline was observed in 45.50% of the cases, and partial recovery was observed in 14.28%. CONCLUSION: We proposed new diagnostic criteria for Pisa syndrome based on previous findings in the literature. Moreover, multiple mechanisms are probably involved in balance control and the development of lateral trunk flexions.

[The state of mucociliary transport of the mucous membrane of the inferior turbinates in children after various types of vasotomy]. / Sostoyanie mukotsiliarnogo transporta slizistoi obolochki nizhnikh nosovykh rakovin u detei posle razlichnykh vidov vazotomii.

The article presents the results of a study that included 127 children aged 8 to 17 years with a diagnosis of turbinate hypertrophy. The children are divided into three groups depending on the chosen vasotomy method. The methods of vasotomy were determined, after which there was a faster restoration of mucociliary clearance of the mucous membrane of the lower nasal concha.

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

BACKGROUND: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. OBJECTIVES: Our goal was to investigate the effects of genetic variants on risk and time to LID. METHODS: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. RESULTS: We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21-2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09-1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (ORfourth_quartile = 1.27; 95% CI, 1.03-1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HRthird_quartile = 1.38; 95% CI, 1.07-1.79; P = 0.0128; HRfourth_quartile = 1.38; 95% CI = 1.06-1.78; P = 0.0147). CONCLUSIONS: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Management of Dysfunctional Gallbladder Disease and the Role of Laparoscopic Cholecystectomy on Symptom Improvement: A Retrospective Cohort Study.

Background Biliary dyskinesia (BD) is a disorder characterised by abdominal pain of biliary origin (i.e., sudden steady pain at the right upper quadrant of the abdomen or the epigastrium, the absence of gallstones on ultrasound (US)), and a decreased gallbladder ejection fraction (GBEF) on a cholecystokinin-cholescintigraphy hepatobiliary iminodiacetic acid (CCK-HIDA) scan. Patients experiencing symptoms suggestive of biliary obstruction, but lacking gallstones, yet exhibiting abnormal gallbladder emptying, may find therapeutic benefit from laparoscopic cholecystectomy. Common symptoms include recurrent, intense, and enduring pain, often exacerbated by fatty food consumption, localised in the upper right quadrant or epigastric region. This pain may radiate to the back or shoulder, persisting for at least 30 minutes but not exceeding several hours, and it is sometimes accompanied by nausea and vomiting. Abnormal gallbladder emptying is typically indicated by a GBEF below 35% on cholescintigraphy following cholecystokinin administration. Objective This study represents a single-centric review focusing on 88 patients over a five-year period who presented with features of dysfunctional gallbladder and underwent cholescintigraphy. The primary aim was to identify whether there is any role for laparoscopic cholecystectomy in symptom improvement among these patients. Methods This was a retrospective cohort study involving data collection using electronic medical records. Eighty-eight patients who underwent the HIDA scan between January 2019 and December 2023 at Wirral University Teaching Hospital NHS Foundation Trust (WUTH) were identified and separated into two groups, either hypofunctioning gallbladder (EF<35% ) or hyperfunctioning gallbladder (EF>80%). Normal HIDA scan patients (EF between 35%-80%) were excluded. The frequency of laparoscopic cholecystectomy and subsequent symptom improvement were recorded. Results Fifty-one patients were diagnosed with gallbladder dyskinesia (BD). Of these, 36 patients (30 females, mean age 43) were diagnosed with hypofunctional gallbladder (EF<35%), where 17 patients underwent laparoscopic cholecystectomy, resulting in symptom improvement in 10 patients (58.8%). Conversely, 15 patients were diagnosed with hyperfunctional gallbladder (13 females, mean age 48.6). Only two patients (13%) underwent laparoscopic cholecystectomy with 100% symptom improvement in both patients. Conclusions In conclusion, our retrospective study highlights the significance of the HIDA scan in identifying gallbladder hypofunction among patients presenting with biliary symptoms. The findings establish the efficacy of laparoscopic cholecystectomy as a management approach, with a notable proportion of patients experiencing symptom improvement (58.8%). These results contribute to our understanding of biliary dysfunction management and emphasise the importance of individualised treatment strategies for optimal patient outcomes. Further, randomised controlled trials (RCTs) are warranted to validate these findings and explore additional factors influencing symptom resolution in this patient population.

Paroxysmal movement disorders.

Paroxysmal movement disorders include two groups of intermittent neurologic disorders: paroxysmal dyskinesia, in which episodes of involuntary hyperkinetic movements (mainly chorea and/or dystonia) occur with preserved consciousness, and episodic ataxias, which are characterized by discrete attacks of cerebellar dysfunction, sometimes associated with progressive ataxia. Since episodic ataxias are individually discussed in Chapter 8 of this volume, we herein provide a deep overview of phenotypic, genetic, pathophysiologic, diagnostic, and treatment aspects of paroxysmal dyskinesia, following the trigger-based nomenclature which distinguishes paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia, and paroxysmal exercise-induced dyskinesia. Emerging paroxysmal dyskinesia not fulfilling the criteria for the above-mentioned subtypes will also be discussed. Phenotypic and genotypic overlap among paroxysmal movement disorders, epilepsy, and migraine have progressively emerged, thus shedding light on a shared pathophysiologic framework. Advances in our understanding of the pathomechanisms underlying paroxysmal movement disorders, which involve dysfunctions of ion channels, proteins associated with the vesical synaptic cycle machinery, and proteins involved in neuronal energy metabolism, point toward a discrete number of converging pathophysiologic pathways and may lay foundations for developing target-specific therapies.

Characterization of pathogenic genetic variants in Russian patients with primary ciliary dyskinesia using gene panel sequencing and transcript analysis.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a group of rare genetically heterogeneous disorders caused by defective cilia and flagella motility. The clinical phenotype of PCD patients commonly includes chronic oto-sino-pulmonary disease, infertility, and, in about half of cases, laterality defects due to randomization of left-right body asymmetry. To date, pathogenic variants in more than 50 genes responsible for motile cilia structure and assembly have been reported in such patients. While multiple population-specific mutations have been described in PCD cohorts from different countries, the data on genetic spectrum of PCD in Russian population are still extremely limited. RESULTS: The present study provides a comprehensive clinical and genetic characterization of 21 Russian families with PCD living in various country regions. Anomalies of ciliary beating in patients` respiratory epithelial cells were confirmed by high-speed video microscopy. In the most cases, custom-designed panel sequencing allowed to uncover causative variants in well-known or rarely mentioned PCD-related genes, including DNAH5, DNAH11, CFAP300, LRRC6, ZMYND10, CCDC103, HYDIN, ODAD4, DNAL1, and OFD1. The variations comprised common mutations, as well as novel genetic variants, some of which probably specific for Russian patients. Additional targeted analysis of mRNA transcripts from ciliated cells enabled us to specify functional effects of newly identified genetic variants in DNAH5 (c.2052+3G>T, c.3599-2A>G), HYDIN (c.10949-2A>G, c.1797C>G), and ZMYND10 (c.510+1G>C) on splicing process. In particular, the splice site variant c.2052+3G>T, detected in four unrelated families, resulted in skipping of exon 14 in DNAH5 transcripts and, according to haplotype analysis of affected probands, was proposed as an ancestral founder mutation in Udmurt population. CONCLUSIONS: The reported data provide a vital insight into genetic background of primary ciliary dyskinesia in the Russian population. The findings clearly illustrate the utility of gene panel sequencing coupled with transcriptional analysis in identification and clinical interpretation of novel genetic variants.