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This teaching review aims to provide an overview of the current approach to children with cerebral palsy (CP), retrieving the best available evidence and summarizing existing knowledge in the field of CP in children. We also highlight areas where more research is needed and novel strategies for diagnosing and treating cerebral palsy. CP includes a group of permanent disorders of movement and posture that cause activity limitation. Multiple risk factors, occurring preconceptionally, prenatally, perinatally, or postneonatally, are involved in the pathogenesis of CP, with the prenatal ones accounting for 80–90 % of cases. Due to its heterogeneity, CP has various classifications, but usually is classified based on clinical findings and motor impairment. Standardized function classification systems have been developed to address inconsistencies in previous classifications. The combination of clinical assessment and validated predictive tools is recommended for an early diagnosis, which is important for early intervention and prevention of secondary impairments. The therapeutic regimen in CP involves prevention and management of the motor and associated problems. It includes the enhancement of motor performance, the enrichment of cognition and communication skills, the prevention of secondary impairments, and the support of parents and caregivers. The care of CP children demands a multidisciplinary approach focused on improving motor skills, reducing comorbidities, enhancing the quality of life, and prolonging survival. • Factors that act alone or additively in the causal paths of Cerebral Palsy. • Clinical reasoning and validated diagnostic tools for an early diagnosis. • Patterns in neuroimaging predictive of cerebral palsy. • Traditional classification supported by Standardized functional systems. • The management of cerebral palsy based on a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

We investigated differences in somatosensory profiles (SSPs) assessed by quantitative sensory testing in children and adolescents with cerebral palsy (CCP) with and without chronic pain and compared these differences to those in a group of typically developed children and adolescents (TDC) with and without chronic pain. All included subjects were consecutively recruited from and tested at the same outpatient orthopedic clinic by the same investigator. The subjects had their reaction times tested. The SSP consisted of the following tests: warmth (WDT), cool (CDT), mechanical (MDT), and vibration (VDT) detection thresholds; heat (HPT), pressure (PPT), and mechanical (MPT) pain thresholds; wind-up ratio (WUR); dynamic mechanical allodynia (DMA) and cold pressor test (CPT) using a conditioned pain modulation (CPM) paradigm. We included 25 CCP and 26 TDC. TDC without chronic pain served as controls. In TDC with chronic pain, WDT, HPT, HPT intensity, and PPT were higher than in controls. No differences in SSPs between CCP with and without chronic pain were observed. In CCP, the MDT, WDT, CDT, and HPT intensity were higher than in controls. CCP had longer reaction times than TDC. There were no differences regarding the remaining variables. In CCP, the SSPs were independent of pain status and findings on MR images. In all CCP the SSPs resembled TDC with chronic pain, compared to TDC without chronic pain. This suggests that CCP do not have the normal neuroplastic adaptive processes that activate and elicit functional changes in the central and peripheral nervous systems. • Chronic pain in children and adolescents with cerebral palsy is an important issue • Somatosensory profiles can be assessed by quantitative sensory testing • No differences between subjects with CP with and without chronic pain • Subjects with CP resemble subjects without CP with chronic pain • Subjects with CP might be preconditioned to chronic pain [ABSTRACT FROM AUTHOR]

Despite the established efficacy of glycopyrronium bromide in reducing drooling among children with neurodevelopmental disabilities, evidence on its impact on the daily lives of children and parents and effectiveness in a real-world setting are scarce, especially among long-term users. This study explored timing and duration of glycopyrronium treatment, effect and impact on daily life, and occurrence of side effects to inform clinical practice. This was a retrospective cohort study at a national referral centre for drooling, including 61 children with nonprogressive neurodevelopmental disabilities, treated with glycopyrronium for anterior and/or posterior drooling between 2011 and 2021. Data were obtained from medical records and supplemented by structured telephone interviews with parents. Anterior drooling severity decreased in 82% of the included children. Changes in the impact of drooling on burden of care, social interaction, and self-esteem were reported in 55%, 31%, and 36%, respectively. Side effects were noted for 71% of cases, yet only 36% of parents deemed these as outweighing the positive impact of treatment. A substantial majority (77%) of the included children were long-term users (≥6 months). Among these, 38% of parents reported decreasing effectiveness and 27% noticed more prominent side effects over time. Glycopyrronium demonstrated potential in mitigating the impact of drooling on daily life, although variations were observed in the specific aspects and extent of improvement. The real-world context of our study provides important insights for refining clinical practices, emphasizing the need for balanced consideration of treatment benefits and potential side effects to facilitate shared decision-making. • Long-term glycopyrronium use, beyond 24 weeks, is prevalent among included children. • Glycopyrronium showed potential to mitigate the impact of drooling in daily life. • Changes in impact were contingent on drooling severity and varied across individuals. • Side effects were common yet expectable, emphasizing the need for close monitoring. [ABSTRACT FROM AUTHOR]

Primary symptoms of cerebral palsy (CP), such as spasm and weakness, can lead to secondary musculoskeletal problems. Exploring the interplay and impact of secondary symptoms is essential in CP management. A total of 56 children (32 males and 24 females) aged eight to 12 years in level I to III of Gross Motor Function Classification System (GMFCS) completed The Pediatric Balance Scale and Wong-Baker Faces Scale and the Posture and Postural Ability Scale. Relationships between the three groups were examined using the Kruskal-Wallis test, Tukey test, gamma coefficient, De Somers D, phi coefficient, Cramér V, and one-way analysis of variance. There was a significant correlation between balance and postural asymmetry (P < 0.001), and no significant difference in balance was there between the severe and moderate asymmetry groups (P = 0.759) and between the mild asymmetry and no asymmetry groups (P = 0.374). Furthermore, there was a significant relationship between postural asymmetry and each of the variables of pain (P < 0.001) and gross motor function (P = 0.002). Although a meaningful correlation was identified between balance and gross motor function (P < 0.001), the relationship between postural asymmetry and balance in GMFCS levels was not found (P = 0.052, P = 0.052, P = 0.233). Conversely, no significant relationship was detected between pain and gross motor function (P = 0.072). Postural asymmetry negatively impacts balance and correlates with pain intensity. Addressing postural problems can contribute to pain management and improved balance. [ABSTRACT FROM AUTHOR]

The majority of the estimated 50 to 100 million children living with disability worldwide reside in low- or middle-income countries. As families migrate to avoid humanitarian crises, children with developmental disability and delay warrant particular attention in refugee and international health settings. During transitions, medical documentation may be lost and diagnoses may not be fully understood, contributing to the challenges of determining etiologies of motor impairment. Of the first 100 refugee children who were referred to the Child Development Clinic, we identified a subset of children referred for motor impairment or cerebral palsy. Data on their presentation, diagnoses following evaluation, and therapeutic services required was collected by retrospective chart review. Twenty children were referred for motor impairment and cerebral palsy. Average age was 8.9 years; 45% were female. Eight children were eventually diagnosed with cerebral palsy, and 12 had alternate or inconclusive diagnoses. Microcephaly was more common in children diagnosed with cerebral palsy. The frequent differences between referral and final diagnoses in refugee children referred for cerebral palsy highlights the need for pediatricians' careful examination and diagnostic reasoning upon initial presentation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the postoperative course and long-term functional and aesthetic outcomes in patients with Beckwith-Wiedemann syndrome (BWS) following surgical reduction of macroglossia, using multiple questionnaires. Patients with BWS who underwent keyhole reduction for macroglossia were included in this study. The postoperative course for each patient was recorded, and multiple questionnaires were administered to evaluate aesthetic concerns, oral incompetence or feeding difficulties, sleep-disordered breathing symptoms, and speech. Nine patients underwent ten reduction glossoplasty surgeries. The mean age at surgery was 22 months. The postoperative course for each case was uneventful, except for one patient who had wound dehiscence. The questionnaires revealed significant improvements in tongue appearance, feeding, drooling, facial appearance, and psychosocial outcomes. There was also a significant reduction in sleep-disordered breathing symptoms after surgery. Keyhole reduction glossoplasty is a safe and effective procedure for the treatment of macroglossia in BWS patients, with excellent functional and aesthetic outcomes and a low complication rate. [ABSTRACT FROM AUTHOR]

The semi-quantitative scale of structural brain Magnetic Resonance Imaging (sqMRI) is a valid and reliable measure of brain lesion extent in children with cerebral palsy (CP) >3-years. This system scores lesion burden for each major brain region. The sum of the scores gives a global score ranging from 0 to 48. To investigate how sqMRI scores changed from infancy to school-age, and whether these were associated with lesion load, age at first assessment, and gross motor function and its changes. Twenty-eight children with CP underwent MRI and motor (Gross Motor Function Measure-66; GMFM-66) assessments when <40-months and again when 8-12-years. We investigated whether (i) toddler/preschool-age sqMRI scores (Time 1) reflected school-age sqMRI scores (Time 2); (ii) temporal changes in sqMRI scores (Time 1–Time 2 difference) were related to the child's age at Time 1 and lesion extent; (iii) early or later sqMRI scores were associated with motor functioning; (iv) sqMRI scores' longitudinal changes were associated with motor changes. Except for the corticosubcortical (grey-matter only) layers, sqMRI scores were significantly higher ('higher lesion load') at Time 1 than at Time 2. Age at Time 1 was not associated with temporal changes in global sqMRI scores. Higher lesion load at Time 2, but not at Time 1, was associated with smaller temporal changes in the global sqMRI score. The sqMRI scores were associated with concurrent, but not future or past motor GMFM-66 scores. Longitudinal changes in sqMRI scores were not associated with longitudinal changes in motor GMFM-66 scores. sqMRI scores of brain lesion extent at school-age are lower and a better indication of later-life motor functioning than very early life sqMRI scores. It may be best to interpret MRI white matter lesions with caution in very early life due to possible changes in lesion appearance and the unpredictable role of functional plasticity. • White matter lesions can be overestimated in children younger than 40-months of age. • Larger lesions at school-age are associated with smaller sqMRI score changes over time. • SqMRI scores are associated with concurrent motor function. • SqMRI scores changes over time are not associated with gross motor function changes. [ABSTRACT FROM AUTHOR]

The goal of this case-control observational study was to compare the levels of the human nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing-3 (NLRP3) protein in the saliva and gingival crevicular fluid (GCF) of patients with symptomatic irreversible pulpitis (SIP) and healthy controls. The 16 patients in the control group were matched with the 16 patients in the SIP group to create a total of 32 patients. In addition to saliva, GCF (n = 48) samples were collected from the involved tooth (n = 16), contralateral tooth (n = 16), and adjacent tooth (n = 16) in the SIP group. Saliva and GCF were taken from the healthy group as a baseline. An independent t -test was used for statistical analysis. The random-intercept model was used to compare the average NLRP3 levels in the SIP tooth, adjacent tooth, and contralateral tooth taking age as a covariate, and the P value was adjusted using Bonferroni correction. There were significantly higher levels of NLRP3 in the saliva of SIP patients (1.78 ± 1.14 ng/ml) compared to the healthy control (0.70 ± 0.70 ng/ml) and in the GCF of the involved tooth (5.72 ± 0.63 ng/ml) compared to healthy people (1.60 ± 0.42 ng/ml) (P <.001). In SIP patients the mean difference of NLRP3 levels between SIP and contralateral teeth was significant at 4.13 ng/ml (95% confidence interval, 3.52–4.70 P <.001) and a mean difference between adjacent teeth and contralateral teeth was significant at 3.53 ng/ml [95% confidence interval, 2.94–4.12 P <.001]. The NLRP3 in GCF and saliva had a negative association in the affected tooth but a negligible correlation in healthy controls. The NLRP3 inflammasome has the potential to be employed as a molecular diagnostic biomarker for pulpal disorders. [ABSTRACT FROM AUTHOR]

The treatment of epiphora has undergone tremendous change in the past, and minimally invasive techniques are being preferred over traditional surgical options. One of them is the use of Inj Botulinum toxin, but there are very few studies that have explored its role in treating post-traumatic epiphora. This study was undertaken to find out the safety and efficacy of injection Botulinum toxin in treating epiphora due to canalicular obstruction following trauma. A longitudinal interventional study was done, and a total of 50 patients were recruited. All patients were subjected to Inj Botulinum toxin in the lacrimal gland (10 units). The study was done for a period of 6 months, and patients were followed up for a period of another 6 months. Changes in Munk score, Schirmer test, and tear meniscus height were considered the main outcome measures. In our study, there were 38 males and 12 females. The age of the patients varied from 24 yrs to 67 yrs. Inj Botulinum toxin was found to be effective in 80% (n = 40/50) of cases as they reported a reduction in watering from eyes after administration of this injection. The complication associated with this treatment was minimal in our study as four patients reported diplopia, whereas two patients developed Ptosis that resolved spontaneously within two months. Inj Botulinum toxin was found to be effective in epiphora caused by canalicular obstruction due to trauma. This treatment should be considered as an alternative treatment modality as it often leads to satisfactory reduction in epiphora in patients with less complications compared to surgical intervention. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is the most common motor disability of childhood, and yet the role of child neurologists and neurodevelopmentalists (CN/NDDs) in the management of children with CP is unclear. Although previous surveys showed that CN/NDDs believe they are uniquely expert in CP motor phenotyping and should be involved in CP management, others have demonstrated that training in CP management among CN/NDD residency programs is inadequate. In this article, we surveyed a group of CN/NDDs at the Child Neurology Society Cerebral Palsy Special Interest Group meeting on January 27, 2022. Questions addressed provider comfort with CP tone management including motor phenotyping, pharmacologic and surgical management, barriers and solutions to improving practice, and the use of systems-based care. Responses from 42 participants demonstrated that CN/NDDs lack experience with CP tone management, with 48% and 58% of respondents reporting little to no experience in pharmacologic or surgical management, respectively. Primary barriers identified to improving comfort with CP tone management included lack of knowledge and ineffective treatment options, while most solutions centered on improving collaborations between CN/NDDs and other specialties. Only 50% of respondents reported currently using systems-based care in the management of patients with CP. An interdisciplinary, systems-based care model would allow for collaboration and knowledge sharing between involved specialties and provide high-value goal-directed care to maximize the functional outcomes for every individual with CP. [ABSTRACT FROM AUTHOR]

In recent years, scientific researchers have increasingly become interested in noninvasive sampling methods for therapeutic drug monitoring and disease diagnosis. As a result, dried saliva spot (DSS), which is a sampling technique for collecting dried saliva samples, has been widely used as an alternative matrix to serum for the detection of target molecules. Coupling the DSS method with a highly sensitive detection instrument improves the efficiency of the preparation and analysis of biological samples. Furthermore, dried blood spots, dried plasma spots, and dried matrix spots, which are similar to those of the DSS method, are discussed. Compared with alternative biological fluids used in dried spot methods, including serum, tears, urine, and plasma, saliva has the advantage of convenience in terms of sample collection from children or persons with disabilities. This review aims to provide integral strategies and guidelines for dried spot methods to analyze biological samples by illustrating several dried spot methods. Herein, we summarize recent advancements in DSS methods from June 2014 to March 2021 and discuss the advantages and disadvantages of the key aspects of this method, including sample preparation and method validation. Finally, we outline the challenges and prospects of such methods in practical applications. Dried blood spot (DBS), dried urine spot (DUS) and dried matrix spot (DMS) have shown to be useful tools to measure analyte in blood, urine and various biological fluids. These methods have same advantages of ease of sample collection, transportation and storage, simplicity of pretreatment and requiring small sample volume. Moreover, a new sampling method, dried saliva spot (DSS), is used as an alternative noninvasive specimen to plasma and urine. And there are some differences between DSS and abovementioned methods, including saliva collection is not restricted anytime and anywhere, low invasiveness compared to other biological samples, readily accepted by children and patients, and reflect the plasma free drug concentration. In addition, all aspects of the DSS, including sample collection, selection of an appropriate filter paper types and filter paper cutting tool, sample preparation, advantages and challenges, will be extensively discussed. [Display omitted] • Use of dried saliva spots (DSS) in drug monitoring and disease diagnosis is reviewed. • Advantages and limitations of the development of the DSS methods are discussed. • Different matrices used in the dried spot method were compared with those of DSS. • Feasibility and prospects of DSS in clinical diagnosis are outlined. [ABSTRACT FROM AUTHOR]

Cestrum axillare poisoning causes significant economic losses in farms of ruminant production due to a fatal acute hepatic disease. The consumption of C. axillare occurs on farms or pastures with a scarcity of feed or with dry forage. Epidemiological, clinical, and pathological data of poisoning outbreaks by C. axillare from 1953 to 2021 in grazing ruminants in southeastern Brazil are reported. A total of 68 bovines, two buffaloes, and two goats exhibited clinical signs and resulted in death due to C. axillare consumption, with 79% of the cases occurring during the dry period. Clinical signs were apathy, anorexia, ruminal arrest, arched back, and constipation with hard stools, sometimes with blood or mucus. Cases with neurological signs due to hepatic encephalopathy showed excitement, aggressiveness, drooling, staggering, and muscle tremors. The pathological findings included hepatocellular necrosis in the liver and microcavitations in the brain's white matter (status spongiosus). The hepatotoxins, carboxyparquin and parquin, were detected in C. axillare leaf samples collected from paddocks grazed by cattle in three southeastern Brazilian municipalities where outbreaks of C. axillare poisoning occurred. This is the first report of parquin and carboxyparquin in C. axillare. [Display omitted] • Cestrum axillare is a cause of centrilobular hepatocellular necrosis in ruminants. • This is the first report of the hepatotoxins, carboxyparquin and parquin, in Cestrum axillare. • Spontaneous poisoning occurred in cattle, buffalo and goats, mainly in the Southeast region of Brazil. • 79% of the poisoning outbreaks occurred during the dry season, during which C. axillare supports green leaves. • To prevent severe losses, it is essential to plan for supplemental herd nutrition in ruminants during the dry season. [ABSTRACT FROM AUTHOR]

Drooling is a troublesome condition, especially in children with neuromuscular and intellectual disability. Over the past decade, novel interventions have been trialled to alleviate drooling in the affected children. Kinesio tape (KT) application has shown promising results in controlling drooling in children. We reviewed the literature to determine the outcome of KT application in drooling children. A literature search was conducted from January 1, 1990 to March 2024 by searching several databases over a 1-month period (April 2024) according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was defined as the success of the intervention determined by the improvement or resolution of symptoms, and the secondary outcome was determined by adjunct or repeated procedures and the presence of complications. Overall, 172 children from 10 studies were identified. All studies included are retrospective studies (Level III). This review included 172 children, with a mean age of 8.2 years (Male: 58.7 %). All included children had underlying comorbidities (100 %), with neurological disorders (77 %) being the most prevalent. KT application was performed predominantly over the orbicularis oris in 6 studies, 118 children[68.6 %], suprahyoid region in 3 studies, 45 children (26.2 %) and multiregion over the head and neck in 1 study of children (5.2 %). Drooling was assessed subjectively in all 100 % of children with objective measurement performed in 3 studies. KT was the only intervention in 40.7 % of the included children, whereas KT was performed in combination with oromotor therapy in 48 children, speech therapy in 44 children, and manipulation therapy in 10 children. All included children (100 %) reported improvement in drooling. No studies reported adverse reactions to KT application. KT application is a safe, effective alternative for drooling children. The effect of KT, however, may be temporary. The quality of the evidence is inadequate to recommend widespread use of the intervention until a better-quality study has been completed. Future randomised controlled studies with a large sample size are warranted to determine the efficacy of this intervention among children. [ABSTRACT FROM AUTHOR]

Emerging research shows that children and young adults (CYAs) with cerebral palsy (CP) are at higher risk for attention-deficit/hyperactivity disorder (ADHD). However, little is known about the clinical and functional characteristics of CYAs with these co-occurring disorders. To estimate associations between a diagnosis of ADHD among CYAs with CP and clinical and functional characteristics. This retrospective, cross-sectional study used data from the electronic health records of CYAs (aged 4–26 years) with CP (n = 1145). We used bivariate and multivariable analyses to estimate associations between an ADHD diagnosis, CP type, Gross Motor Function Classification System (GMFCS) level, speech or language disorder, and intellectual disability. 18.1 % of CYAs with CP had a diagnosis of ADHD. CYAs with spastic-bilateral CP had lower odds of ADHD (adjusted odds ratio [AOR] = 0.58; 95 % confidence interval [CI], 0.35–0.96). Odds of having ADHD were significantly lower for those with GMFCS levels III-V (AOR = 0.10; 95 % CI, 0.06–0.15). Our study found that a diagnosis of ADHD among CYAs with CP was associated with greater clinical and functional impairments compared to counterparts without ADHD. Findings highlight the need to screen for both conditions because of the high comorbidity rates in this population. • Prevalence of ADHD is higher in children and young adults (CYAs) with CP. • CYAs with spastic-bilateral CP had lower odds of an ADHD diagnosis. • Odds of ADHD were lower for those with severe physical limitations. [ABSTRACT FROM AUTHOR]

Over 50 % of children and youth with cerebral palsy (CP) experience mental health challenges, with anxiety and depression most common. Youth with CP also experience several physiological symptoms such as fatigue, pain, sedentary lifestyle, and sleep disturbances that impact their daily living; however, little is known about the impact of these symptoms on mental health outcomes in these youth. This study addressed this gap and examined the individual and cumulative impacts of physiological symptoms on anxiety and depression symptoms in youth with CP. Forty youth with CP aged 8 to 18 years, and their caregiver, participated in this cross-sectional observational study. Pain, fatigue, anxiety, and depressive symptoms were measured using caregiver- and self-reported questionnaires and participants wore accelerometers for seven consecutive days, providing non-invasive physical activity and sleep pattern data. Youth with CP experienced substantial physiological symptoms and elevated anxiety and depression symptoms. Linear regression models determined that all physiological factors were predictive of caregiver-reported youth anxiety (R 2 = 0.23) and youth depressive symptoms (R 2 = 0.48). Fatigue, pain severity, sleep efficiency, and physical activity outcomes individually and cumulatively contributed to caregiver-reported youth anxiety and depression symptoms. These findings highlight the important role of physiological symptoms as potential risk factors and potential targets for intervention for mental health issues for in youth with CP. • Children with CP experienced pain, fatigue, disordered sleep, and low levels of physical activity. • Children with CP experienced elevated symptoms of anxiety and depression. • Linear regressions determined all physiological factors contributed to caregiver-related anxiety and depression symptoms. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) dysfunction is a common non-motor feature of Parkinson disease (PD). GI symptoms may start years before the onset of motor symptoms and impair quality of life. Robust clinical trial data is lacking to guide screening, diagnosis and treatment of GI dysfunction in PD. To develop consensus statements on screening, diagnosis, and treatment of GI dysfunction in PD. The application of a modified Delphi panel allowed for the synthesis of expert opinions into clinical statements. Consensus was predefined as a level of agreement of 100 % for each item. Five virtual Delphi rounds were held. Two movement disorders neurologists reviewed the literature on GI dysfunction in PD and developed draft statements based on the literature review. Draft statements were distributed among the panel that included five movement disorder neurologists and two gastroenterologists, both experts in GI dysmotility and its impact on PD symptoms. All members reviewed the statements and references in advance of the virtual meetings. In the virtual meetings, each statement was discussed, edited, and a vote was conducted. If there was not 100 % consensus, further discussions and modifications ensued until there was consensus. Statements were developed for screening, diagnosis, and treatment of common GI symptoms in PD and were organized by anatomic segments: oral cavity and esophagus, stomach, small intestine, and colon and anorectum. These consensus recommendations offer a practical framework for the diagnosis and treatment of GI dysfunction in PD. • Maintain vigilance with screening for GI symptoms at regular follow-up visits across all disease stages. • Consider the impact of PD motor medications (and non-PD medications) on GI symptoms. • A multidisciplinary approach to GI dysfunction in PD is the ideal practice. • Refer to gastroenterology for esophageal dysphagia, persistent bothersome symptoms that are refractory to initial interventions or accompanied by red flags. [ABSTRACT FROM AUTHOR]

Pain perception mechanisms in cerebral palsy remain largely unclear. This study investigates brain activity in adults with cerebral palsy during painful and non-painful stretching to elucidate their pain processing characteristics. Twenty adults with cerebral palsy and 20 controls underwent EEG in three conditions: rest, non-painful stretching, and painful stretching. Time-frequency power density of theta, alpha, and beta waves in somatosensory and frontal cortices was analyzed, alongside baseline pressure pain thresholds. Cerebral palsy individuals exhibited higher theta, alpha, and beta power density in both cortices during painful stretching compared to rest, and lower during non-painful stretching. Controls showed higher power density during non-painful stretching but lower during painful stretching. Cerebral palsy individuals had higher pain sensitivity, with those more sensitive experiencing greater alpha power density. These findings confirm alterations in the cerebral processing of pain in individuals with cerebral palsy. This knowledge could enhance future approaches to the diagnosis and treatment of pain in this vulnerable population. [Display omitted] • Individuals with cerebral palsy show higher EEG power density than controls during painful stretching. • In individuals with cerebral palsy, alpha power density in painful stretching negatively correlates with their pain sensitivity. • Individuals with cerebral palsy show lower EEG power density than controls during non-painful stretching. [ABSTRACT FROM AUTHOR]

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disease (MND), and sialorrhea is a known symptom in patients with ALS, which may cause a social embarrassment and discomfort. However, people do not pay attention to sialorrhea up to now. This study is aimed at conducting a systematic review and meta-analysis of the pooled prevalence of sialorrhea in ALS patients all around the world and raising awareness of salivation.Methods: We searched PubMed and EMBASE databases to obtain the comprehensive literatures which reported the prevalence of sialorrhea. We used AHRQ and NOS to evaluate the literature quality. Subgroup analyses were performed based on screening instruments and severity of sialorrhea. At the meantime, sensitivity analyses was also conducted to identify the source of heterogeneity.Results: A total of 17 eligible studies which included 21 groups of data reported prevalence of sialorrhea. The pooled prevalence of sialorrhea among ALS patients was 30.8% (95% CI: 20.0%-44.2%). For studies using ALSFRS-R, direct questioning, postal survey, and ALSSoL average and ALSFRS-R, the pooled prevalence of sialorrhea was 22.7%, 25.8%, 29.8% and 52.0% respectively. According to the severity of sialorrhea, the prevalence of mild, moderate, and severe sialorrhea were 25.1%, 11.2%, and 10.5%, respectively. And none of the studies alone had a significant effect on the overall prevalence of sialorrhea after we eliminated each study separately in sensitivity analyses.Conclusions: Sialorrhea is a relatively common symptom in ALS patients with a comparatively high prevalence. In our study, we found that the prevalence of sialorrhea in ALS patients is relatively higher than the results based on direct questioning or postal survey. Therefore, we deduced that sialorrhea should be evaluated by more complex professional assessment scales to improve the quality of life and improve early prognosis of disease. [ABSTRACT FROM AUTHOR]

• Mainly functional HRQOL domains are affected in survivors of head and neck cancer. • Psychological HRQOL domains are affected less, except following major surgery. • The most significant negative predictor for HRQOL is bone resection. • Functional aspects of HRQOL frequently remain affected over time. • Psychological disability is usually present after treatment but resolves over time. Long-term health-related quality of life (HRQOL) is frequently affected in head and neck cancer (HNC) survivors. Due to the shortage of studies investigating long-term patient-reported outcomes, we investigated long-term HRQOL using the novel FACE-Q HNC Module. A retrospective cross-sectional single-center study was performed, including all patients who underwent curative treatment for HNC between 2006 and 2013. All eligible patients (n = 863) were invited to participate of whom 540 completed the questionnaires. Additionally, a prospective longitudinal cohort of 43 HNC patients treated between 2020 and 2022 was included who preoperatively filled in the FACE-Q, and at three, six, and 12 months postoperatively. HRQOL domain scores were analyzed to visualize group characteristics by tumor site and type of surgical resection. Both surgical and non-surgical HNC treatments predominantly affected long-term functional HRQOL domains (eating, salivation, speech, and swallowing), eating distress, and speaking distress, with distinct profiles depending on tumor site and type of treatment. In contrast, few long-term intergroup differences between HNC patients were observed for appearance, smiling, drooling distress, and smiling distress. Longitudinal data showed significant deterioration across all functional HRQOL domains in the short-term following treatment. Patients predominantly reported long-lasting negative treatment effects at 12 months follow-up for functional domains, whereas psychological domains showed near-complete recovery at group level. At long-term, various function-related and psychosocial HRQOL domains still are affected in head and neck cancer survivors. The results may serve to better inform patients with regard to specific treatments and highlight HRQOL domains which may potentially be optimized. [ABSTRACT FROM AUTHOR]

Sialorrhea is a common neurological manifestation of Parkinson's disease (PD). No specifically designed prospective study has tested the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on sialorrhea in patients with advanced PD. We focused on the effect of STN-DBS on the incidence of sialorrhea in patients with PD. This multicenter, prospective, non-randomized concurrent clinical trial analyzed the incidence of sialorrhea during long-term follow-up in 170 patients with advanced PD (84 patients with STN-DBS and 86 patients with medication therapy). After STN-DBS, 58.1% of patients presented with sialorrhea (Drooling Rating Scale (DRS) > 5) compared with 39.3% of patients with medication therapy (P < 0.001). STN-DBS stimulation demonstrated a significant increase in DRS and Drooling Severity and Frequency Scale (DSFS) compared with the patients with medication therapy (P < 0.001). At follow-up, the onabotulinumtoxin-A (BTX-A) injection ratio was significantly higher in the STN-DBS group (29.8% vs. 11.9%, P = 0.0057) compared with the patients with medication therapy. STN-DBS increased the risk of sialorrhea in patients with advanced PD. clinicaltrials. gov (NCT06090929) • Patients with STN-DBS were more susceptible to sialorrhea. • The sialorrhea were more likely to deteriorate after DBS during long-term follow-up. • Botox injection effectively improved sialorrhea in patients after STN-DBS. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess tolerance of botulinum toxin A injection into the salivary glands under local anesthesia in a pediatric population. Secondary endpoints comprised efficacy and side-effects. A retrospective observational study included children treated between January 2013 and March 2020 for sialorrhea and/or pharyngeal salivary congestion. Children were identified from the botulinum toxin A injection database. The study included 162 injection sessions in 55 children. Injections were performed under local anesthesia with nitrous oxide, after clinical location of the site. Epidemiological and clinical data, injection tolerance on the FLACC scale, treatment response and complications were recorded. For submandibular gland injections, pain was absent in 81 cases, mild in 64, moderate in 4 and intense in 1. In parotid gland injections, pain was absent in 45 cases, mild in 89, moderate in 17 and intense in 1. Injection tolerance was significantly poorer (P < 0.005) in parotid than submandibular glands. Seventy-seven percent of the injections had a positive effect on sialorrhea. Fifteen patients presented transient adverse events: mainly dysphagia and paradoxical increase in sialorrhea. Salivary gland botulinum toxin A injections in under local anesthesia were well-tolerated, safe and effective for children with sialorrhea and/or pharyngeal salivary congestion. [ABSTRACT FROM AUTHOR]

To evaluate relationships between spontaneous swallowing frequency, dysphagia, and drooling in children with cerebral palsy. Spontaneous swallowing frequency was predicted to be inversely related to both dysphagia and drooling among children with cerebral palsy. A secondary objective compared patterns among spontaneous swallowing frequency, drooling, and age in healthy children vs children presenting with cerebral palsy. Cross sectional study. Children with cerebral palsy were tested at a Cerebral Palsy Reference Center in a university hospital. Healthy children were tested in their home setting. Twenty children with cerebral palsy were recruited from the local registry for cerebral palsy children and purposive sampling among parents. A group of 30 healthy children was recruited by purposive sampling among family, friends, and the local community. Children below 1 year of age up to 5 years of age were included in the healthy group. This age range was targeted to maximize the potential for drooling in this group. Both groups provided data on spontaneous swallowing frequency (swallows per minute, or SPM), dysphagia, and drooling. Motor impairment was documented in the children with cerebral palsy. SPM was significantly lower in children with cerebral palsy. Among children with cerebral palsy, SPM correlated significantly with dysphagia severity and trended toward a significant correlation with drooling at rest. In this subgroup, SPM was not correlated with age or degree of motor impairment. Dysphagia was significantly correlated with drooling at rest and both dysphagia and drooling at rest were correlated with degree of motor impairment. The 2 groups did not differ in the degree of drooling at rest. Among healthy children, age but not SPM demonstrated a significant inverse correlation with drooling quotient at rest. Spontaneous swallowing frequency is related to dysphagia and drooling in children with cerebral palsy. The pattern of relationships among spontaneous swallowing frequency and drooling is different between children with cerebral palsy and younger healthy children. [ABSTRACT FROM AUTHOR]

In this case series with retrospective review we compared the outcomes of patients with sialorrhoea who had a submandibular excision (SE) alone and those who had submandibular excision with parotid duct ligation (SE + PL) between 2012 and 2018. Primary endpoints of complication rates and caregivers' perceptions of success were collected. A total of 41 submandibular excisions were performed for sialorrhoea (26 patients underwent SE, while 15 underwent SE + PL). Significant differences in the groups existed at baseline with patients in the SE plus PL group being more likely to have a tracheostomy (p = 0.015), to use sublingual atropine (p = 0.038) and respiratory medications (albuterol p = 0.0075, gentamicin p = 0.018), to have more pneumonias six months prior to the procedure (p < 0.001), and more hospitalisations six months prior to the procedure (p = 0.046). More postoperative surgical site complications were associated with ligation (p = 0.012). There was no difference in systemic infection (p = 0.25), and no difference in caregivers' perceptions of success in reducing sialorrhoea (18/24 SE compared with 10/14 SE + PL, p = 1.00). There were more surgical site complications in those undergoing SE plus PL than in those who had SE alone. Given this data, parotid duct ligation may not yield additional benefit when combined with submandibular excision. [ABSTRACT FROM AUTHOR]

Over 80% of patients undergoing radiotherapy (RT) for head and neck cancer (HNC) suffer reduced saliva secretion and dry mouth symptoms due to salivary gland damage. Although therapeutic interventions to alleviate such RT-induced damage are available, long-term hypofunction remains a significant issue. Therefore, novel therapeutic solutions to prevent irradiation (IR)-induced salivary gland damage are required. This study explored the protective effect of inorganic nitrate in preventing IR-induced salivary gland injury via pyroptosis suppression, both in vivo and in vitro. In the treatment group, C57BL/6 mice were pretreated with 2 mmol/L NaNO 3 supplied in drinking water one week before a single-dose of 15 Gy IR in the submandibular gland (SMG) region. Human vein endothelial cells (HUVECs) and mice SMG cells were treated with 10 μmol/L or 100 μmol/L NaNO 3 2 h before a single-dose of 8 Gy IR. In vivo , IR-induced decreased saliva flow rate and body weight loss could be alleviated by nitrate supplementation. Nitrate prevented acinar and microvascular endothelial cell loss. Moreover, nitrate improved mitochondrial function and significantly decreased pyroptosis-related indexes. In vitro , nitrate supplementation reduced reactive oxygen species (ROS) generation by preserving mitochondrial homeostasis to inhibit NLPR3 inflammasome-mediated pyroptosis both in HUVECs and SMG cells. Nitrate showed potential as an oral protective agent to prevent IR-induced salivary gland damage; prospective insight into the underlying molecular mechanisms is presented. [Display omitted] • Patients treated with radiotherapy for HNC suffer salivary gland damage. • We explored nitrate protective effect against IR-induced salivary gland injury. • HUVECs and mice SMG cells were treated with NaNO 3 before a single dose of 8 Gy IR. • In vivo, nitrate prevented the loss of acinar cells and microvascular endothelial cells. • In vitro, nitrate supplement inhibited NLPR3 inflammasome-mediated pyroptosis. [ABSTRACT FROM AUTHOR]

Background: Drooling is a clinically relevant non-motor symptom of people with Parkinson's disease (PwP). Several drooling rating scales are available. Nevertheless, the compelling scientific evidence supporting their validity is limited. This study aims to evaluate clinical rating scales for drooling, assessing their characteristics, clinimetric properties, and clinical utility classification.Methods: A systematic review was undertaken. Two reviewers performed independent literature searches using the CENTRAL®, CINAHL®, Embase®, MEDLINE®, SciElo®, and SPEECH BITE® databases. We used consensus-based standards for the selection of health measurement instruments (COSMIN) and the International Parkinson's disease and the Movement Disorders (MDS) criteria to evaluate the included rating scales.Results: The following six rating scales were identified: Drooling Impact Scale (DIS), Sialorrhea Scoring Scale (SSS), Drooling Severity and Frequency Scale (DSFS), Drooling Rating Scale (DRS), Sialorrhea Clinical Scale for Parkinson Disease (SCS-PD), and the Radboud Oral Motor inventory for Parkinson's disease - Saliva (ROMP-saliva). The scales had heterogeneous characteristics: (i) not all were created/adapted for PwP; (ii) different dimensions associated with drooling are assessed; (iii) cross-cultural adaptations are limited to some languages. The clinimetric properties showed: (i) target population size limitations; (ii) incomplete reliability analysis; (iii) lack of robust validity; (iv) sensitivity to change not fully explored. Following the MDS criteria, only one tool was classified as "recommended", the ROMP-saliva.Conclusions: This review provides information for an adequate selection of a drooling rating scale for clinical and/or research purposes. To date, ROMP-saliva is the only scale with substantial evidence of its clinimetric properties adequacy and data in PwP. [ABSTRACT FROM AUTHOR]

Patients that undergo head and neck (H&N) radiation therapy (RT) require laborious delineation of organs-at-risk (OARs) on computed tomography (CT) scans in a treatment planning system (TPS) to minimize radiation to normal tissue. This task can be completed rapidly and accurately with recently developed artificial intelligence-based semantic segmentation models. The current study aims to deploy and evaluate a strategy for improving clinical practice with this technology. Deep learning models were trained and tested with CT scans and OAR contours from previous H&N RT cases at our clinic. Two medical physicists vetted the models and selected a 2.5D U-Net for further implementation. The model was embedded in a dedicated server at the hospital, programmed to read H&N CT scans staged for import into the TPS, generate auto-contours, and write them into a TPS-compatible format made available alongside the scan. In the pilot implementation, the auto-contouring service was utilized for more than 60 cases, prospectively. The auto-contours were quantitatively evaluated against the treatment-approved contours to determine how much modification was performed by the clinical team. The 2.5D U-Net selected for clinical integration segments 21 OARs in less than 3 minutes per scan. Across all the prospective cases, the mean Dice score and mean 95th percentile Hausdorff distance (mm) between the auto-contour and treatment-approved contour for each of the 21 OARs were as follows, respectively: brainstem (0.93, 1.94), optic chiasm (0.70, 2.96), left cochlea (0.69, 2.37), right cochlea (0.68, 2.44), esophagus (0.88, 2.46), left globe (0.93, 1.50), right globe (0.93, 1.63), glottis (0.91, 2.13), larynx (0.93, 2.76), mandible (0.90, 4.86), left optic nerve (0.78, 1.64), right optic nerve (0.82, 1.65), oral cavity (0.86, 8.46), left parotid gland (0.91, 2.78), right parotid gland (0.91, 2.39), pharynx (0.85, 2.39), spinal cord (0.87, 2.27), left submandibular gland (0.85, 3.46), right submandibular gland (0.83, 3.69), left temporal lobe (0.94, 2.20), and right temporal lobe (0.95, 2.09). The auto-contours for the optic chiasm, optic nerves, cochleas, and submandibular glands differed substantially from the final contours, a finding corroborated by the clinical team; the rest were clinically acceptable with minor or no edits necessary. The proposed strategy provides a sophisticated starting point for treatment planning that has garnered overall favorable feedback from the participating radiation oncologists and dosimetrists. Consequently, the technique is being extended to other treatment sites. [ABSTRACT FROM AUTHOR]

The high diagnostic accuracy indices for saliva severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase PCR (RT-PCR) reported in adults has not been demonstrated in children, and adequately powered studies focused on the paediatric population are lacking. This study was carried out to determine the diagnostic accuracy of saliva for SARS-CoV-2 RT-PCR in ambulatory children. During 1 to 23 October 2020, we recruited a population-based sample of children presenting for coronavirus disease 2019 (COVID-19) screening in Dubai, United Arab Emirates. Each child provided paired nasopharyngeal (NP) swab and saliva for SARS-CoV-2 RT-PCR N, E and RdRp gene detection. Paired NP swab and saliva samples were obtained from 476 children with mean ± standard deviation age of 10.8 ± 3.9 years, and 58.2% were male (277/476). Nine participants were sampled twice, so 485 pairs of NP swab/saliva were tested. Virus detection in at least one specimen type was reported in 17.9% (87/485), with similar detection in NP swab (16.7%, 81/485) and saliva (15.9%, 77/485). Sensitivity and specificity of saliva RT-PCR was 87.7% (95% confidence interval (CI) 78.5–93.9) and 98.5% (95% CI 96.8–99.5). The positive and negative predictive values were 92.2% (95% CI 84.2–96.3) and 97.6% (95% CI 95.7–98.6), with a kappa coefficient of 0.879 (95% CI 0.821–0.937). Concordance of findings between NP swab and saliva did not differ by age (p 0.67) or gender (p 0.29). Cycle threshold (Ct) values were significantly higher in NP swab/saliva pairs with discordant findings compared to those with both specimens positive. In light of these findings, we recommend saliva as a diagnostic specimen for COVID-19 screening in children. [ABSTRACT FROM AUTHOR]

Genetic selection for improved climatic resilience is paramount to increase the long-term sustainability of high-producing dairy cattle, especially in face of climate change. Various physiological indicators, such as rectal temperature (RT), respiration rate score (RR), and drooling score (DS), can be used to genetically identify animals with more effective coping mechanisms in response to heat stress events. In this study, we investigated genetic parameters for RT, RR (score from 1–3), and DS (score from 1–3). Furthermore, we assessed the genetic relationship among these indicators and other economically important traits for the dairy cattle industry. After data editing, 59,265 (RT), 30,290 (RR), and 30,421 (DS) records from 13,592 lactating Holstein cows were used for the analyses. Variance components were estimated based on a multiple-trait repeatability animal model. The heritability ± standard error estimate for RT, RR, and DS was 0.06 ± 0.01, 0.04 ± 0.01, and 0.02 ± 0.01, respectively, whereas their repeatability was 0.19, 0.14, and 0.14, respectively. Moderate genetic correlations of RR with RT and DS (0.26 ± 0.11 and 0.25 ± 0.16) and nonsignificant correlation between RT and DS (−0.11 ± 0.14) were observed. Furthermore, the approximate genetic correlations between RT, RR, and DS with 12 production, 29 conformation, 5 fertility and reproduction, 5 health, and 9 longevity-indicator traits were assessed. In general, the approximate genetic correlations calculated were low to moderate. In summary, 3 physiological indicators of heat stress response were measured in a large number of animals and shown to be lowly heritable. There is a value in developing a selection index including all the 3 indicators to improve heat tolerance in dairy cattle. All the unfavorable genetic relationships observed between heat tolerance and other economically important traits can be accounted for in a selection index to enable improved climatic resilience while also maintaining or increasing productivity in Holstein cattle. [ABSTRACT FROM AUTHOR]

X-linked dystonia-parkinsonism (XDP) is a progressive neurodegenerative disorder that has been studied well in recent years. This scoping review aimed to describe the current state of knowledge about the diagnosis and treatment of XDP, to provide clinicians with a concise and up-to-date overview. We conducted a scoping review of pertinent literature on the diagnosis and treatment of XDP using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. There were 24 articles on diagnostic methods and 20 articles on therapeutic interventions for XDP, with 7 review articles describing both. The detection of the SVA retrotransposon insertion within the TAF1 gene is confirmatory for XDP. Oral medications are marginally effective. Chemodenervation with botulinum toxin is an effective treatment. Pallidal deep brain stimulation (DBS) has been shown to provide significant improvement in the dystonia and quality of life of patients with XDP for a longer time. A less invasive surgical option is the transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS), which has shown promising effects with the limited number of case reports available. XDP is a geneti disorder characterized by striatal symptoms and pathology on neuroimaging. No effective oral medications are available for the management of XDP. The use of botulinum toxin is limited by its cost and duration of effects. As of now, pallidal DBS is deemed to be the best option. Another promising option is the tcMRgFUS but still has limited studies on its safety and efficacy in XDP. • X-linked dystonia-parkinsonism (XDP) is a genetic neurodegenerative disorder, with an SVA retrotransposon insertion within the TAF1 gene. • No effective oral medications are available for the management of XDP. • Botulinum toxin use is limited by its cost and duration of effects. • Pallidal deep brain stimulation provides significant improvement in the dystonia and quality of life of patients with XDP. • Transcranial magnetic resonance-guided focused ultrasound is a promising option. [ABSTRACT FROM AUTHOR]

Botulinum toxin (BoNT) was approved by the United States Food and Drug Administration (FDA) in 1989 for facial movement disorders and strabismus, but since that time its indications have been expanding beyond neurologic and ophthalmologic disorders. This article is a narrative review of the therapeutic use of BoNT in tremors, dystonia, sialorrhea, bladder and other autonomic symptoms, levodopa-induced dyskinesia and other problems occuring in the setting of parkinsonism. Though FDA approval is lacking for some of these indications, expert experiences have shown that BoNT is often beneficial in this group of patients. • This is an updated and comprehensive review on the use of botulinum toxin in parkinsonism. • In this updated manuscript, we discuss the use of botulinum toxin in parkinsonian tremor in greater detail. • We have also included in our discussion some of the latest publications on this topic. [ABSTRACT FROM AUTHOR]

The objectives of the study were to use a heat stress scoring system to evaluate the severity of heat stress on dairy cows using different heat abatement techniques. The scoring system ranged from 1 to 4, where 1 = no heat stress; 2 = mild heat stress; 3 = severe heat stress; and 4 = moribund. The accuracy of the scoring system was then predicted using 3 machine learning techniques: logistic regression, Gaussian naïve Bayes, and random forest. To predict the accuracy of the scoring system, these techniques used factors including temperature-humidity index, respiration rate, lying time, lying bouts, total steps, drooling, open-mouth breathing, panting, location in shade or sprinklers, somatic cell score, reticulorumen temperature, hygiene body condition score, milk yield, and milk fat and protein percent. Three different treatments, namely, portable shade structure, portable polyvinyl chloride pipe sprinkler system, or control with no heat abatement, were considered, where each treatment was replicated 3 times with 3 second-trimester lactating cows. Results indicate that random forest outperformed the other 2 methods, with respect to both accuracy and precision, in predicting the sprinkler group's score. Both logistic regression and random forest were consistent in predicting scores for control, shade, and combined groups. The mean probability of predicting non-heat-stressed cows was highest for cows in the sprinkler group. Finally, the logistic regression method worked best for predicting heat-stressed cows in control, shade, and combined. The insights gained from these results could aid dairy producers to detect heat stress before it becomes severe, which could decrease the negative effects of heat stress, such as milk loss. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effectiveness of ablating postganglionic parasympathetic fibers of the submandibular ganglion in combination with sublingual gland excision in the treatment of primary sialorrhea. Healthy volunteers were initially chosen to determine a basic saliva flow rate value by saliva collection. Next, unstimulated and stimulated saliva flow rates, and a visual analog scale index for sialorrhea were recorded in all the patients pre- and postoperatively. In addition, the generalized anxiety disorder scale was used to assess preoperative anxiety symptoms. The follow-up durations ranged from 24 to 36 months after surgery. A total of 10 patients were included in this study. Preoperatively, the mean unstimulated saliva flow rate for the 10 patients was 11.26 ± 4.19 ml/10 min, the stimulated saliva flow rate was 16.76 ± 3.49 ml/6 min, and the visual analog scale index was 66.29 ± 14.86. Postoperatively, the mean unstimulated and stimulated saliva flow rates were significantly reduced to 5.99 ± 1.33 ml/10 min (p = 0.001) and 13.28 ± 1.86 ml/6 min (p = 0.013), respectively, and the visual analog scale index was 25.41 ± 5.6 (p < 0.001). No complications were found after operation. This study demonstrates that ablation of postganglionic parasympathetic fibers of the submandibular ganglion in combination with sublingual gland excision by an intraoral approach is a simple, safe, and efficient approach for treating primary sialorrhea. [ABSTRACT FROM AUTHOR]

Drooling, or sialorrhoea, is a common difficulty faced by children with neurological impairment including cerebral palsy. It may lead to a reduction in their quality of life, causing skin irritation, dehydration and high levels of embarrassment and social isolation for both the patient and family. This review will discuss the assessment of patients with sialorrhoea and potential management strategies including conservative management, medical options, botulinum toxin injections and surgery. [ABSTRACT FROM AUTHOR]

• The prevalence of hip migration requiring surgery is 24.3% in children with cerebral palsy. • The most advanced cases are not for the oldest children. • Hips of most children remain stable over time (up to 5 years). • Pelvic obliquity and hip migration are probably linked. • Three trajectories of hip migration may be distinguished. In children with cerebral palsy (CP), we have little information on when hip migration (HM) starts, what causes hip displacement, how HM changes over time, and how to halt this migration to avoid surgery. We aimed to estimate the prevalence of HM percentage (HMP) >4 0% in a homogeneous population of non-ambulant children with CP and model the changes in HMP over a 2.6-year mean follow-up. From September 2009 to September 2015, this observational, prospective, multicenter cohort study recruited 235 children from 51 centers who were 3 to 10 years old and had levels IV and V of the Gross Motor Function Classification System for CP. The outcomes were yearly HMP measurements by the Reimers index. Only children with at least one hip with HMP ≤ 40% at baseline were included in trajectory modeling. Comparisons of chidren's characteristics between trajectory groups were adjusted by the false discovery rate method. The prevalence of children with at least one hip with HMP > 40% was estimated at 24.3% (95% confidence interval 18.6–30.0). Pelvic obliquity was observed in 51.4% and 24.4% of children with asymmetric and symmetric HMP (P = 0.002). The trajectory modelling identified 3 types of MP changes over time. Many children (67.4% and 79.3% for the right and left hip) could be assigned to the "stable" trajectory group. In non-ambulant children with CP, the prevalence of HM requiring surgery is low and most hips remain practically stable over time. [ABSTRACT FROM AUTHOR]

Background: The early identification of cerebral palsy (CP) in the primary care context is often problematic and referral for diagnosis often delayed. This study aimed to identify clinical features associated with the early detection of CP that can be used by the primary care provider.Methods: We performed a scoping review by searching six electronic databases. We included English language articles that addressed the diagnosis of CP and/or its differential diagnosis in children and ways of detecting CP before the diagnosis is established (i.e., early clinical signs of CP) via (1) questions on the patient's clinical history, (2) developmental screening and/or health questionnaires, or (3) physical or neurological examination.Results: Included studies (n = 41; 27 overview studies and 14 original studies) were grouped into the three themes. Most of the overview articles relied on expert opinion, and all original studies included patients at high risk of developing CP. The most commonly identified features from each theme were early hand preference on clinical history, delayed or absent achievement of motor developmental milestones on developmental screening, and persistent primitive reflexes on neurological examination.Conclusions: Overall, the literature on the early observable clinical signs that should prompt referral for investigation of possible CP in the specific context of well-baby care surveillance was sparse and inconsistent. Further research should focus on evaluating the contribution of readily identifiable clinical features. [ABSTRACT FROM AUTHOR]

Background: Botulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks.Methods: Adults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs).Results: In total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by -0.16 and -0.17, respectively, at the end-of-study visit. Subjects' GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%).Conclusions: Data support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks. [ABSTRACT FROM AUTHOR]

The detection of human DNA on and within illicit drug preparations is novel and a focus of current research. Previous studies have indicated that certain drug-related powders present in illicit drug preparations can interfere with downstream DNA analysis when directly added to the PCR. Therefore, it is important to determine if these drug-related powders are effectively removed during the DNA extraction or whether traces of powder remain to interfere with DNA processing. Three extraction methods were selected to assess their efficiency at removing drug-related powders for downstream processes using DNA from both saliva and touch depositions. This is the first study to compare efficiencies of DNA extraction methods from drug-related powders. The extraction methods compared were the DNA IQ™ System, the QIAamp® DNA Investigator Kit and the combination of a simple lysis step followed by use of the Microcon® DNA Fast Flow device. Saliva was added to dimethylsulfone (DMS), nitrostyrene and PROSOLV® tablet mixture to determine the effect of powder type (based on solubility). Saliva was also added to 0, 50, 200 and 400 mg of DMS to determine the effect of an increase in DMS quantity. Trace DNA was deposited onto DMS using a worn glove approach. These samples were re-tested six months post-DNA deposition and profiled for further comparisons. Ten replicates were conducted for each condition with five replicates of saliva positive controls per method (n = 255 samples). A subset of samples was chemically analysed to determine if DMS was present in the final DNA eluant. The readily soluble DMS did not interfere with any of the extraction methods at lower amounts, however increasing the DMS to 400 mg reduced the relative DNA yields using the Microcon® and Investigator methods. The tablet mixture reduced the relative DNA yield of all three methods, however the nitrostyrene (which was relatively insoluble) only reduced the relative DNA yield of the DNA IQ™. The Investigator method performed the best with the trace samples, followed by the Microcon® method and then the DNA IQ™. DMS was detected in all extracts chemically analysed from the DNA IQ™ and Microcon®, whereas only one sample tested from the Investigator kit contained DMS in the extract and was in a relatively low amount compared to the other samples. Not one kit outperformed the others in all comparisons, however the Investigator kit was the most efficient overall at optimising the DNA yield whilst also removing the powders more effectively. • Three extraction methods were compared with three types of drug-related powders. • Performance of each kit dependent on powder type and amount of powder. • QIAamp® DNA Investigator Kit returned best DNA profile from trace amounts of DNA. • QIAamp® DNA Investigator Kit was the most efficient at removing powder from final extract. [ABSTRACT FROM AUTHOR]

There are several types of muscle biopsy inclusions. The most common are filamentous bodies, concentric laminated bodies, hyaline bodies, reducing bodies, tubular aggregates, cytoplasmic bodies, cylindrical spirals, nemaline rods, and mitochondrial paracrystalline inclusions. Rhomboidal-rectangular crystalline inclusions are very rare and they have been previously described in an adult patient with muscle aches, persistently elevated serum creatine kinase, and no molecular characterization. Here we describe a 12-year-old boy that presented motor developmental delay, drooling, lower limbs myalgia aggravated by exercise, and difficulties climbing stairs. He presented asthma, treated with sodium montelukast. He was born of non-consanguineous parents with no affected relatives. Physical examination disclosed diffuse muscle atrophy, winged scapula, lower limbs proximal weakness, waddling gait, inability to walk on the heels, and Gowers maneuver. Electromyogram demonstrated myopathic muscle action potentials. Muscle magnetic resonance imaging demonstrated symmetric adductor magnus, tibialis anterior, extensor digitorum longus, peroneus, and tibialis posterior muscle fat replacement. Transaminases were elevated with AST (TGO) 111 IU/L (14-41)(2.7x), ALT (TGP) 151 IU/L (151) (8-46)(3.3x) and normal gamma-GT 14 U/L (< 50). Muscle enzymes were increased with total creatine kinase (CPK) of 6100 IU/L (< 225)(27.1x), and aldolase 43 U/L (< 15.2)(2.8x). A right vastus lateralis muscle biopsy demonstrated dystrophic features with pronounced variation in fiber caliber, necrosis, phagocytosis, and regeneration. There were rare rimmed vacuoles and small irregular oxidative defects (SDH, NADH, COX). No reducing bodies were observed on menadione-NBT reaction. No ragged red fibers, COX negative fibers or strongly SDH reactive vessels were observed. Immunohistochemistry disclosed regenerating fibers reactive for neonatal myosin and desmin. Normal immunohistochemical reactions were observed for dystrophin (Rod, C-terminus, N-terminus), sarcoglycans (alpha, beta, gamma, delta), caveolin, alpha-2 laminin (merosin), alpha-dystroglycan, collagen VI, telethonin, and emerin. Sarcolemmal dysferlin reaction was strong with rare fibers with slight reduction in intensity. No tubulin antibodies were available for immunohistochemical studies. Toluidine blue semithin sections demonstrated rhomboidal-rectangular structures in 6.2% of the fibers, that were confirmed by Transmission Electron Microscopy. The crystals were electron dense, randomly oriented and not membrane bound. No nemaline bodies, mitochondrial paracrystalline inclusions, central cores or multiminicores were found. A descriptive diagnosis of Congenital muscular dystrophy with rhomboidal-rectangular crystalline inclusions was rendered. This was the only case in a cohort of more than 1700 consecutive muscle biopsies. The ultrastructure of the crystals was similar to the condition previously described as myopathy with tubulin-reactive inclusions. Tubulin is a major component of the microtubules, involved in movements of flagella, organelles, and chromosomes. Microtubules are essential for myotube formation to allow the cells to respond mechanically to the environment. It is believed that the crystals are the result of altered synthesis, processing, or degradation. To the best of our knowledge, this is the first paediatric patient described with Congenital muscular dystrophy with rhomboidal-rectangular crystalline inclusions. This is also the first description of the muscle imaging features of this rare condition. This report expands the phenotypic spectrum of the condition. Scientific collaboration between different centers will be necessary to better characterize this very rare condition. [ABSTRACT FROM AUTHOR]

• BioXtra® significantly reduced the bacterial metabolic activity of the biofilm. • BioXtra® demonstrated its potential to impair biofilm development. • BioXtra® inhibited the multiplication of cariogenic bacteria. • BioXtra® prevented the development of enamel caries. • Chlorhexidine performed better than BioXtra® in all variables assessed. Considering the lack of studies investigating salivary substitutes to control post-radiation caries for patients with head and neck cancer (HNC), this study aimed to evaluate the antibacterial, antibiofilm, and anticaries effects of BioXtra® on the microcosm biofilm formed on different enamel types (non-irradiated and irradiated) and from distinct saliva sources (control and HNC patients). Non-irradiated and irradiated enamel specimens were treated with BioXtra®, phosphate-buffered-saline (PBS; negative control), or 0.12% chlorhexidine (CHX; positive control) for 1 min. Biofilm was produced from human saliva (healthy participants with normal salivary flow for the control group or irradiated HNC patients with hyposalivation for the HNC group), mixed with McBain saliva, under 0.2% sucrose exposure, daily submitted to the treatments (1 min), for 5 days. Bacterial metabolic activity, biofilm viability, CFU counting, and enamel demineralization were determined. BioXtra® significantly reduced the bacterial metabolic activity for both enamel types and the inoculum sources, being more effective for the irradiated enamel or for the saliva from the control group. Similarly, BioXtra® significantly reduced the biofilm viability, the CFU for total microorganisms, mutans streptococci, and lactobacilli, and was able to significantly reduce the mineral loss and the lesion depth compared to PBS. CHX was an effective treatment to significantly reduce all parameters, performing better than BioXtra® and reinforcing its reliable efficiency as a positive control. Regardless of the enamel type and the inoculum source, BioXtra® presented antibacterial, antibiofilm, and anticaries effects under this experimental model, which should be confirmed in further clinical studies. [ABSTRACT FROM AUTHOR]

To describe the effects of salivary gland Botulinum Toxin-A (SG BoNT-A) on children with drooling due to neurological dysfunction. This was a 3½-year prospective observational case series design of children referred for SG BoNT-A injections at a pediatric hospital (2010–2014). Outcomes were parent-reported severity, frequency, impact of drooling, and respiratory morbidity; and, from hospital records, number of respiratory hospital admissions. Out of 17 children treated, complete data were available for 15 (including 8 boys) aged 3–14 years (Mean = 9.9 years; SD = 3.4), with a combined total of 71 injections. Most had cerebral palsy (n = 11), classified as Level V (n = 10) or IV (n = 1) on the Gross Motor Function Classification Scale (GMFCS). In almost all instances, parents reported reductions in severity, frequency, and impact of drooling, and parent-reported respiratory morbidity. Among those with posterior drooling (n = 12), most children (n = 10) did not have advanced respiratory disease. A trend towards reduced respiratory-related hospital admissions was observed during SG BoNT-A treatment periods. SG BoNT-A can improve severity, frequency, and impact of drooling. It can also reduce respiratory-related hospital admissions in children with posterior drooling without advanced respiratory disease. For children with advanced respiratory disease, it may reduce severity and impact of drooling. [ABSTRACT FROM AUTHOR]

To evaluate if drooling recurrence after surgery of the submandibular ducts is due to surgical failure or other variables. Historic cohort with prospective collected data of all patients with severe drooling who underwent unsuccessful submandibular duct surgery with subsequent re-intervention between 2003 and 2018. A reference cohort was used for comparison of clinical variables. Six males and 4 females were included (cerebral palsy n = 8 , neurodevelopmental disorders n = 2). All patients underwent submandibular gland surgery as a primary intervention (duct ligation n = 8 , submandibular duct relocation n = 2) followed by re-intervention (submandibular gland excision n = 7, parotid duct ligation n = 3). One patient underwent tertiary surgery (parotid duct ligation after re-intervention by submandibular gland excision). Three patients were successful after re-intervention. No difference was found between both re-intervention techniques. There was significantly more severe dental malocclusion (50% vs. 21%, P value = 0.047) and severe speech disorders (80% vs. 42%, P value = 0.042) in the current cohort when compared to the reference cohort. Recurrence of drooling surgery is most likely not caused by surgical failure of the primary intervention, because re-intervention (submandibular gland excision) did not lead to more success. Dysarthria and dental malocclusion might negatively influence treatment outcome. [ABSTRACT FROM AUTHOR]

Sialorrhea is a common problem in children with disability, often negatively affecting socialization, self-esteem, and burden of care. Saliva control surgery is an available option to manage this problem, particularly when other conservative methods have failed. As little is known about the long-term impact of surgery, we followed up 62 patients who had combined bilateral submandibular duct translocation and bilateral sublingual gland excision at our pediatric hospital between 1994 and 2014. Eligible individuals were identified through a search of ICD procedure codes. When families of patients were contacted successfully, they were invited to complete a 14-item questionnaire designed specifically for this study. The results indicated that long-term outcomes of surgery were very good; 13/62 (21%) individuals no longer had a drooling problem and another 30 (48%) experienced only mild to moderate drooling. Although 84% families reported some or major improvement in drooling, 9 families reported that they would not go through the experience again because of a difficult recovery period, lack of effectiveness of the intervention, changes in saliva consistency that caused coughing and gagging, and dental decay. None of the collected variables were predictive of good or poor outcome. The study indicated that surgical intervention is effective in the long term in the majority of cases and can be recommended to other families who attend our saliva control clinic. [ABSTRACT FROM AUTHOR]

Botulinum toxin injections are useful in patients with refractory sialorrhoea although the optimum treatment protocol and its efficacy over a long period of follow up are controversial. The aim of our prospective study was to examine the efficacy and complications of a protocol of repeated ultrasound-guided botulinum toxin injections of fixed doses at a tertiary children's hospital. A total of 79 procedures were done in 34 patients who were followed up for two years. The overall complication rate was 3%. The outcome measures considered included the Drooling Frequency Severity Scale (DFSS), visual analogue scale (VAS), and carers' assessments of the reduction in drooling. Our study highlighted two types on non-responders (primary and secondary) of which 3/34 required definitive surgical management. In summary, this study shows that a protocol of repeated injections of fixed doses of botulinum toxin A, while not beneficial in all cases, is a potentially valuable option for the safe and effective treatment of sialorrhoea in children. [ABSTRACT FROM AUTHOR]

• PLCβ3 selectively localizes in the duct system of parotid and sublingual glands. • PLCβ3 is mainly demonstrated inside ductal cell cytoplasm with/without polarity. • PLCβ3 is also localized in intraglandular nerve bundles. • Possible modulatory roles of the PLCβ3 in saliva secretion. Phospholipase C (PLC)β has a role in saliva secretion by controlling intracellular Ca2+ via its product, IP 3. The present study was attempted to localize PLCβ isoforms in mouse salivary glands in situ. A single major band was detected for PLCβ3 in immunoblots of the parotid and sublingual glands (PG, SLG), while no such band was seen in the submandibular gland (SMG). No bands were detected for PLCβ1 or 4 in the three glands. In immuno-light microscopy of PG and SLG, substantial immunoreactivity for PLCβ3 was seen in the cytoplasm including the plasmalemma of almost all ductal cells, while no distinct immunoreactivity was discerned in most acinar cells except for sublingual demilune cells. Numerous ductal cells exhibited higher immunoreactivity for PLCβ3 in their apical/supranuclear cell domain including the plasmalemma than in the basal/infranuclear domain, indicating an apico-basal polarity. In immuno-gold electron microscopy of PG ducts and SLG ducts and demilunes, most gold particles were found in association with plasma membranes as well as various intracellular membranes, most of which formed small oblong or flattened vesicles and vacuoles. A few particles were seen without association with any membranous structures. The present finding supports the previous physio-pharmacological result that Ca2+-signaling proteins as well as initial intracellular Ca2+ changes occur in the apical cell domain including the plasma membranes of the exocrine cells. [ABSTRACT FROM AUTHOR]

Abstract The aim of this study was to explore whether botulinum toxin A (BTXA) injection treats epiphora secondary to submandibular gland (SMG) transplantation for severe keratoconjunctivitis sicca. Fifteen patients with epiphora after SMG transplantation were separated to three groups, and received 15 U, 20 U and 25 U BTXA injection in the transplanted SMG, respectively. Secretion of transplanted SMG was assessed subjectively by visual analogue scale (VAS) regarding epiphora, and objectively by Schirmer test. There were no significant differences in the 15-U BTXA group regarding the values of the VAS on epihora before and 1 month after BTXA injection. While in 20-U group and 25-U group, the values of VAS on epihora decreased significantly after BTXA injection, and lasted for 6 months. Under resting conditions, the secretion of transplanted SMG decreased 64.4%, 73.0% and 78.0% in 15-U, 20-U and 25-U groups, respectively (P < 0.01), in 1 month after BTXA injection; significant secretion decreasing lasted 3 months only in the 25-U BTXA group. BTXA injection can decrease the secretion of transplanted SMG significantly, relieving the symptoms of epiphora; 25 U BTXA is a suitable dose to treat 'opportunistic epiphora' after SMG transplantation. [ABSTRACT FROM AUTHOR]