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BMC Medicine Jun 2024Cerebral palsy (CP), the most common physical disability of childhood, is often accompanied by a range of comorbidities including pain. Pain is highly prevalent in... (Review)
Review
BACKGROUND
Cerebral palsy (CP), the most common physical disability of childhood, is often accompanied by a range of comorbidities including pain. Pain is highly prevalent in children and young people with CP, yet has been poorly understood, inaccurately assessed, and inadequately managed in this vulnerable population. This narrative review presents recent research advances for understanding and managing pain in children and young people with CP, focusing on chronic pain, and highlights future research directions.
MAIN BODY
Pain prevalence rates in CP vary due to different methodologies of studies. Recent systematic reviews report up to 85% of children experience pain; higher in older children, females, and those with dyskinesia and greater motor impairment. Research examining the lived experience perspectives of children and their families demonstrate that even those with mild motor impairments have pain, children want to self-report pain where possible to feel heard and believed, and management approaches should be individualized. Notably, many children with cognitive and communication impairments can self-report their pain if adjustments are provided and they are given a chance. Past inadequacies of pain assessment in CP relate to a focus on pain intensity and frequency with little focus on pain interference and coping, a lack of tools appropriate for the CP population, and an assumption that many children with cognitive and/or communication limitations are unable to self-report. Recent systematic reviews have identified the most reliable and valid assessment tools for assessing chronic pain. Many were not developed for people with CP and, in their current form, are not appropriate for the spectrum of physical, communication, and cognitive limitations seen. Recently, consensus and co-design in partnership with people with lived experience and clinicians have identified tools appropriate for use in CP considering the biopsychosocial framework. Modifications to tools are underway to ensure feasibility and applicability for the spectrum of abilities seen.
CONCLUSION
Recent research advances have improved our understanding of the prevalence, characteristics and lived experience of chronic pain, and refined assessment methods in children and young people with CP. However, the very limited evidence for effective and novel management of chronic pain in this population is where research should now focus.
Topics: Humans; Cerebral Palsy; Chronic Pain; Child; Adolescent; Pain Management; Female; Male
PubMed: 38862988
DOI: 10.1186/s12916-024-03458-0 -
JAMA Network Open Jun 2024
Topics: Humans; Delirium; Emergency Service, Hospital; Male; Female; Aged; Psychomotor Agitation; Middle Aged; Inpatients; Length of Stay; Aged, 80 and over; Hospitalization; Time Factors
PubMed: 38861262
DOI: 10.1001/jamanetworkopen.2024.16343 -
Molecular Genetics & Genomic Medicine Jun 2024Spinocerebellar ataxia 29 (SCA29) is a rare genetic disorder characterized by early-onset ataxia, gross motor delay, and infantile hypotonia, and is primarily associated...
BACKGROUND
Spinocerebellar ataxia 29 (SCA29) is a rare genetic disorder characterized by early-onset ataxia, gross motor delay, and infantile hypotonia, and is primarily associated with variants in the ITPR1 gene. Cases of SCA29 in Asia are rarely reported, limiting our understanding of this disease.
METHODS
A female Korean infant, demonstrating clinical features of SCA29, underwent evaluation and rehabilitation at our outpatient clinic from the age of 3 months to the current age of 4 years. Trio-based genome sequencing tests were performed on the patient and her biological parents.
RESULTS
The infant initially presented with macrocephaly, hypotonia, and nystagmus, with nonspecific findings on initial neuroimaging. Subsequent follow-up revealed gross motor delay, early onset ataxia, strabismus, and cognitive impairment. Further neuroimaging revealed atrophy of the cerebellum and vermis, and genetic analysis revealed a de novo pathogenic heterozygous c.800C>T, p.Thr267Met missense mutation in the ITPR1 gene (NM_001378452.1).
CONCLUSION
This is the first reported case of SCA29 in a Korean patient, expanding the genetic and phenotypic spectrum of ITPR1-related ataxias. Our case highlights the importance of recognizing early-onset ataxic symptoms, central hypotonia, and gross motor delays with poor ocular fixation, cognitive deficits, and isolated cerebellar atrophy as crucial clinical indicators of SCA29.
Topics: Humans; Female; Mutation, Missense; Inositol 1,4,5-Trisphosphate Receptors; Spinocerebellar Degenerations; Child, Preschool; Cerebellar Ataxia; Spinocerebellar Ataxias; Infant
PubMed: 38860480
DOI: 10.1002/mgg3.2466 -
Cureus May 2024Situs inversus totalis (SIT), affecting 1 in 6,000 to 10,000 individuals, involves a complete reversal of chest and abdominal organs. About one-third of SIT cases...
Situs inversus totalis (SIT), affecting 1 in 6,000 to 10,000 individuals, involves a complete reversal of chest and abdominal organs. About one-third of SIT cases coincide with primary ciliary dyskinesia, leading to diverse symptoms. Surgical challenges arise in procedures like liver transplantation and biliary interventions due to organ abnormalities. This case study explores cholecystitis in a patient with SIT, offering insights crucial for navigating complexities in treating this congenital anomaly. A 34-year-old Arab female, who was a known SIT case, came to the hospital complaining of abdominal pain in the left upper quadrant. After conducting a chest X-ray and an abdominal ultrasound, the patient was diagnosed with cholecystitis. She then underwent a planned cholecystectomy to remove her gallbladder. SIT presents challenges when it comes to procedures such as laparoscopic cholecystectomy (LC). Nevertheless, the proficiency of skilled surgeons, meticulous preoperative planning, and strict adherence to surgical principles render the execution of LC on patients with SIT both achievable and secure. The successful completion of over 120 cases serves as evidence of the adaptability and precision that can be achieved through surgery for individuals with SIT.
PubMed: 38860076
DOI: 10.7759/cureus.59957 -
Ear, Nose, & Throat Journal Jun 2024Patients with chronic rhinosinusitis (CRS) that is refractory to maximal medical and surgical therapy should be evaluated for other primary conditions. Cystic fibrosis...
Patients with chronic rhinosinusitis (CRS) that is refractory to maximal medical and surgical therapy should be evaluated for other primary conditions. Cystic fibrosis (CF), primary immunodeficiency (PID), and primary ciliary dyskinesia (PCD) are potential risk factors for refractory CRS. These conditions present with variable disease severity and diagnosis may be delayed into adulthood. We report a case of a mother-daughter pair with CRS refractory to maximal medical management. The patients were further evaluated and found to have features consistent with CF, PID, and PCD. All 3 are rare disorders and thought to cause CRS in isolation. Patients with refractory CRS should be further evaluated to identify alternative diagnoses and ensure proper management. Refractory CRS may be multifactorial, with different risk factors simultaneously contributing to its persistence.
PubMed: 38855824
DOI: 10.1177/01455613241261563 -
Tremor and Other Hyperkinetic Movements... 2024The tremor characteristics of patients with spinocerebellar ataxia 12 (SCA12) are often likened to those in patients with essential tremor (ET); however, data are...
BACKGROUND
The tremor characteristics of patients with spinocerebellar ataxia 12 (SCA12) are often likened to those in patients with essential tremor (ET); however, data are sparse, and videotaped tremor examinations are rare.
CASE REPORT
A 37-year-old woman with progressive hand and head tremors underwent genetic testing after conventional diagnostics failed to explain her symptoms. A variation confirmed spinocerebellar ataxia type 12 (SCA12), a condition not previously considered because classical cerebellar signs were absent. The tremor characteristics of this patient differed in numerous respects from those seen in patients with ET.
DISCUSSION
Although often likened to ET, under careful scrutiny, the tremor characteristics observed in this patient with SCA12 were inconsistent with those typically seen in ET. Such discrepancies highlight the necessity of careful phenotyping for tremor disorders, particularly in familial cases. Recognizing the specific tremor phenomenology of SCA12 and distinguishing it from ET is crucial to avoid misdiagnosis and to guide appropriate management and familial counseling.
HIGHLIGHTS
This report characterizes in detail an early-stage SCA12 patient initially misdiagnosed as essential tremor, underscoring the importance of nuanced clinical assessment and genetic testing in atypical tremor cases. Similar patients should be meticulously phenotyped to prevent misclassification and enhance our understanding of tremor pathophysiology.
Topics: Humans; Female; Adult; Spinocerebellar Ataxias; Essential Tremor; Phenotype; Tremor; Diagnosis, Differential
PubMed: 38854909
DOI: 10.5334/tohm.889 -
Neurobiology of Disease Aug 2024Parkinson's disease is caused by a selective vulnerability and cell loss of dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal...
Parkinson's disease is caused by a selective vulnerability and cell loss of dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal dopamine depletion. In Parkinson's disease therapy, dopamine loss is counteracted by the administration of L-DOPA, which is initially effective in ameliorating motor symptoms, but over time leads to a burdening side effect of uncontrollable jerky movements, termed L-DOPA-induced dyskinesia. To date, no efficient treatment for dyskinesia exists. The dopaminergic and serotonergic systems are intrinsically linked, and in recent years, a role has been established for pre-synaptic 5-HT1a/b receptors in L-DOPA-induced dyskinesia. We hypothesized that post-synaptic serotonin receptors may have a role and investigated the effect of modulation of 5-HT4 receptor on motor symptoms and L-DOPA-induced dyskinesia in the unilateral 6-OHDA mouse model of Parkinson's disease. Administration of RS 67333, a 5-HT4 receptor partial agonist, reduces L-DOPA-induced dyskinesia without altering L-DOPA's pro-kinetic effect. In the dorsolateral striatum, we find 5-HT4 receptor to be predominantly expressed in D2R-containing medium spiny neurons, and its expression is altered by dopamine depletion and L-DOPA treatment. We further show that 5-HT4 receptor agonism not only reduces L-DOPA-induced dyskinesia, but also enhances the activation of the cAMP-PKA pathway in striatopallidal medium spiny neurons. Taken together, our findings suggest that agonism of the post-synaptic serotonin receptor 5-HT4 may be a novel therapeutic approach to reduce L-DOPA-induced dyskinesia.
Topics: Animals; Dyskinesia, Drug-Induced; Levodopa; Oxidopamine; Mice; Male; Mice, Inbred C57BL; Serotonin 5-HT4 Receptor Agonists; Antiparkinson Agents; Corpus Striatum; Receptors, Serotonin, 5-HT4; Parkinsonian Disorders; Pyridines; Neurons; Piperidines; Pyrimidines
PubMed: 38852753
DOI: 10.1016/j.nbd.2024.106559 -
Stem Cell Research Aug 2024Spinocerebellar Ataxia Type 7 (SCA7) is an autosomal dominantly inherited disorder, primarily characterized by cerebellar ataxia and visual loss. SCA7 is caused by a CAG...
Spinocerebellar Ataxia Type 7 (SCA7) is an autosomal dominantly inherited disorder, primarily characterized by cerebellar ataxia and visual loss. SCA7 is caused by a CAG repeat expansion in exon 3 of the ATXN7 gene. We generated human induced pluripotent stem cells (hiPSCs) from peripheral blood-derived erythroblasts from two SCA7 patients (LUMCi051-A,B and LUMCi052-A,B,C) using integration-free episomal vectors. All hiPSC clones express pluripotency factors, show a normal karyotype, and can differentiate into the three germ layers. These lines can be used for in vitro disease modeling and therapy testing.
Topics: Humans; Induced Pluripotent Stem Cells; Spinocerebellar Ataxias; Cell Line; Male; Cell Differentiation; Female; Adult
PubMed: 38851031
DOI: 10.1016/j.scr.2024.103462 -
Frontiers in Immunology 2024Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and... (Review)
Review
BACKGROUND
Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown.
CASE PRESENTATION
Here, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment's efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L.
CONCLUSION
We present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.
Topics: Humans; Female; Middle Aged; Autoantibodies; Contactin 1; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Recurrence; Tremor; Plasmapheresis
PubMed: 38846936
DOI: 10.3389/fimmu.2024.1368487 -
Clinical Parkinsonism & Related... 2024Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture....
Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture. Problems can arise due to impaired movement ability (hypokinesias), e.g. nocturnal hypokinesia or early-morning akinesia, or to excessive movement (hyperkinesias), e.g. end-of-the-day dyskinesia, parasomnias, periodic limb movement during sleep and restless legs syndrome. These disorders can have a significant negative impact on the sleep, daytime functional ability, and overall quality of life of individuals with PD and their carers. The debilitating motor issues are often accompanied by a combination of non-motor symptoms, including pain and cramping, which add to the overall burden. Importantly, nocturnal motor disorders encompass a broader timeline than just the period of sleep, often starting in the evening, as well as occurring throughout the night and on awakening, and are not just limited to problems of insomnia or sleep fragmentation. Diagnosis can be challenging as, in many cases, the 'gold standard' assessment method is video polysomnography, which may not be available in all settings. Various validated questionnaires are available to support evaluation, and alternative approaches, using wearable sensors and digital technology, are now being developed to facilitate early diagnosis and monitoring. This review sets out the parameters of what can be considered normal nocturnal movement and describes the clinical manifestations, usual clinical or objective assessment methods, and evidence for optimal management strategies for the common nocturnal motor disorders that neurologists will encounter in people with PD in their clinical practice.
PubMed: 38845753
DOI: 10.1016/j.prdoa.2024.100258