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BMC Neurology Jul 2023People with stroke generally experience abnormal muscle activity and develop balance disorder. Based on the important role of the proximal joints of the lower extremity... (Randomized Controlled Trial)
Randomized Controlled Trial
The hip joint mobilization with movement technique improves muscle activity, postural stability, functional and dynamic balance in hemiplegia secondary to chronic stroke: a blinded randomized controlled trial.
BACKGROUND
People with stroke generally experience abnormal muscle activity and develop balance disorder. Based on the important role of the proximal joints of the lower extremity in balance maintenance, hip joint mobilization with movement technique can be applied to enhance normal joint arthrokinematics. Therefore, the present study aimed to investigate the effectiveness of hip joint mobilization with movement technique on stroke patients' muscle activity and balance.
METHODS
Twenty patients aged between 35 and 65 years old with chronic stroke were randomly assigned either to an experimental group (n = 10) or to a control group (n = 10). Both groups participated in a 30-minute conventional physiotherapy session 3 times per week for 4 weeks. The experimental group received an additional 30-minute's session of hip joint mobilization with movement technique on the affected limb. The muscle activity, berg balance scale, time up and go, and postural stability were measured at baseline, 1-day and 2-week follow-up by a blinded assessor.
RESULTS
The experimental group showed a significant improvement in berg balance scale, time up and go, and postural stability (p ≤ 0.05). The rectus femoris, tibialis anterior, biceps femoris, and medial gastrocnemius muscles' activations of the affected limb during static balance test markedly changed along with the biceps femoris, erector spine, rectus femoris, and tibialis anterior muscles during dynamic balance test after hip joint mobilization with movement technique. The mean onset time of rectus abdominus, erector Spine, rectus femoris, and tibialis anterior muscles activity significantly decreased in the affected limb after hip joint mobilization with movement technique compared to the control group (p ≤ 0.05).
CONCLUSIONS
The results of the present study suggest that a combination of hip joint mobilization with movement technique and conventional physiotherapy could improve muscle activity and balance among chronic stroke patients.
TRIAL REGISTRATION NUMBER
The study was registered in the Iranian Registry of Clinical Trials (No; IRCT20200613047759N1). Registration date: 2/08/2020.
Topics: Humans; Adult; Middle Aged; Aged; Hemiplegia; Iran; Stroke; Quadriceps Muscle; Brain Damage, Chronic; Hip Joint; Physical Therapy Modalities
PubMed: 37434123
DOI: 10.1186/s12883-023-03315-2 -
Circulation. Arrhythmia and... Jul 2023The cryoballoon (CB) represents the gold standard single-shot device for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Single-shot pulsed...
BACKGROUND
The cryoballoon (CB) represents the gold standard single-shot device for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Single-shot pulsed field PVI ablation (nonthermal, cardiac tissue selective) has recently entered the arena. We sought to compare procedural data and long-term outcome of both techniques.
METHODS
Consecutive AF patients who underwent pulsed field ablation (PFA) and CB-based PVI were enrolled. CB PVI was performed using the second-generation 28-mm CB; PFA was performed using a 31/35-mm pentaspline catheter. Success was defined as freedom from atrial tachyarrhythmia after a 3-month blanking period.
RESULTS
Four hundred patients were included (56.5% men; 60.8% paroxysmal AF; age 70 [interquartile range, 59-77] years), 200 in each group (CB and PFA), and baseline characteristics did not differ. Acute PVI was achieved in 100% of PFA and in 98% (196/200) of CB patients (=0.123; 4 touch-up ablations). Median procedure time was significantly shorter in PFA (34.5 [29-40] minutes) versus CB (50 [45-60] minutes; <0.001), fluoroscopy time was similar. Overall procedural complications were 6.5% in CB and 3.0% in PFA (=0.1), driven by a higher rate of phrenic nerve palsies using CB. The 1-year success rates in paroxysmal AF (CB, 83.1%; PFA, 80.3%; =0.724) and persistent AF (CB, 71%; PFA, 66.8%; =0.629) were similar for both techniques.
CONCLUSIONS
PFA compared with CB PVI shows a similar procedural efficacy but is associated with shorter procedure time and no phrenic nerve palsies. Importantly, 12-month clinical success rates are favorable but not different between both groups.
Topics: Male; Humans; Aged; Female; Atrial Fibrillation; Follow-Up Studies; Treatment Outcome; Pulmonary Veins; Cryosurgery; Paralysis; Catheter Ablation; Recurrence
PubMed: 37254781
DOI: 10.1161/CIRCEP.123.011920 -
Pathology Dec 2023Enterovirus D68 (EV-D68) is one of hundreds of non-polio enteroviruses that typically cause cold-like respiratory illness. The first EV-D68 outbreak in the United States... (Review)
Review
Enterovirus D68 (EV-D68) is one of hundreds of non-polio enteroviruses that typically cause cold-like respiratory illness. The first EV-D68 outbreak in the United States in 2014 aroused widespread concern among the public and health authorities. The infection was found to be associated with increased surveillance of acute flaccid myelitis, a neurological condition that causes limb paralysis in conjunction with spinal cord inflammation. In vitro studies utilising two-dimensional (2D) and three-dimensional (3D) culture systems have been employed to elucidate the pathogenic mechanism of EV-D68. Various animal models have also been developed to investigate viral tropism and distribution, pathogenesis, and immune responses during EV-D68 infection. EV-D68 infections have primarily been investigated in respiratory, intestinal and neural cell lines/tissues, as well as in small-size immunocompetent rodent models that were limited to a young age. Some studies have implemented strategies to overcome the barriers by using immunodeficient mice or virus adaptation. Although the existing models may not fully recapitulate both respiratory and neurological disease observed in human EV-D68 infection, they have been valuable for studying pathogenesis and evaluating potential vaccine or therapeutic candidates. In this review, we summarise the methodologies and findings from each experimental model and discuss their applications and limitations.
Topics: Humans; Animals; United States; Mice; Enterovirus D, Human; Neuromuscular Diseases; Myelitis; Paralysis; Enterovirus Infections
PubMed: 37852802
DOI: 10.1016/j.pathol.2023.08.007 -
Journal of Neurology Dec 2023Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S. HypoPP can present with different phenotypes:...
BACKGROUND AND OBJECTIVES
Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S. HypoPP can present with different phenotypes: periodic paralysis (PP), permanent muscle weakness (PW), and mixed weakness (MW) with both periodic and permanent weakness. Little is known about the natural history of HypoPP.
METHODS
In this 3-year follow-up study, we used the MRC scale for manual muscle strength testing and whole-body muscle MRI (Mercuri score) to assess disease progression in individuals with HypoPP-causing mutations in CACNA1S.
RESULTS
We included 25 men (mean age 43 years, range 18-76 years) and 12 women (mean age 42 years, range 18-76 years). Two participants were asymptomatic, 21 had PP, 12 MW, and two PW. The median number of months between baseline and follow-up was 42 (range 26-52). Muscle strength declined in 11 patients during follow-up. Four of the patients with a decline in muscle strength had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis. Fat replacement of muscles increased in 27 patients during follow-up. Eight of the patients with increased fat replacement had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis.
DISCUSSION
The study demonstrates that HypoPP can be a progressive myopathy in both patients with and without attacks of paralysis.
Topics: Male; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Hypokalemic Periodic Paralysis; Follow-Up Studies; Mutation; Muscle Weakness; Paralysis
PubMed: 37656291
DOI: 10.1007/s00415-023-11964-z -
Neurotherapeutics : the Journal of the... Mar 2024The tauopathies encompass over 20 adult neurodegenerative diseases and are characterized by the dysfunction and accumulation of insoluble tau protein. Among them,... (Review)
Review
The tauopathies encompass over 20 adult neurodegenerative diseases and are characterized by the dysfunction and accumulation of insoluble tau protein. Among them, Alzheimer's disease, frontotemporal dementia, and progressive supranuclear palsy collectively impact millions of patients and their families worldwide. Despite years of drug development using a variety of mechanisms of action, no therapeutic directed against tau has been approved for clinical use. This raises important questions about our current model of tau pathology and invites thoughtful consideration of our approach to nonclinical models and clinical trial design. In this article, we review what is known about the biology and genetics of tau, placing it in the context of current and failed clinical trials. We highlight potential reasons for the lack of success to date and offer suggestions for new pathways in therapeutic development. Overall, our viewpoint to the future is optimistic for this important group of neurodegenerative diseases.
Topics: Humans; tau Proteins; Alzheimer Disease; Tauopathies; Supranuclear Palsy, Progressive; Neurodegenerative Diseases
PubMed: 38278659
DOI: 10.1016/j.neurot.2024.e00321 -
Frontiers in Endocrinology 2023Pathogenic heterozygous variants in cause a rare monogenic form of osteoporosis known as calvarial doughnut lesions with bone fragility (CDL). The clinical... (Review)
Review
Pathogenic heterozygous variants in cause a rare monogenic form of osteoporosis known as calvarial doughnut lesions with bone fragility (CDL). The clinical presentations of -related bone pathology range from childhood-onset osteoporosis with low bone mineral density and sclerotic doughnut-shaped lesions in the skull to a severe spondylometaphyseal dysplasia with neonatal fractures, long-bone deformities, and short stature. In addition, neurological manifestations occur in some patients. encodes sphingomyelin synthase 2 (SMS2), an enzyme involved in the production of sphingomyelin (SM). This review describes the biochemical structure of SM, SM metabolism, and their molecular actions in skeletal and neural tissue. We postulate how disrupted SM gradient can influence bone formation and how animal models may facilitate a better understanding of -related osteoporosis.
Topics: Animals; Child; Humans; Infant, Newborn; Facial Nerve; Osteoporosis; Paralysis; Skull; Sphingomyelins; Transferases (Other Substituted Phosphate Groups)
PubMed: 37886644
DOI: 10.3389/fendo.2023.1224318 -
Brain : a Journal of Neurology Aug 2023The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the...
The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer's disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 ± 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression.
Topics: Male; Humans; Middle Aged; Aged; Female; Parkinsonian Disorders; Supranuclear Palsy, Progressive; Multiple System Atrophy; Magnetic Resonance Imaging; United Kingdom
PubMed: 36975168
DOI: 10.1093/brain/awad105 -
MBio Aug 2023Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in...
Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic diversity of EV-D68 since 2014, although the virus was discovered in the 1960s. The mechanisms by which EV-D68 targets the central nervous system are unknown. Since enteroviruses are human pathogens that do not routinely infect other animal species, establishment of a human model of the central nervous system is essential for understanding pathogenesis. Here, we describe two human spinal cord organoid (hSCO)-based models for EV-D68 infection derived from induced, pluripotent stem cell (iPSC) lines. One hSCO model consists primarily of spinal motor neurons, while the another model comprises multiple neuronal cell lineages, including motor neurons, interneurons, and glial cells. These hSCOs can be productively infected with contemporary strains, but not a historic strain, of EV-D68 and produce extracellular virus for at least 2 weeks without appreciable cytopathic effect. By comparison, infection with hSCO with another enterovirus, echovirus 11, causes significant structural destruction and apoptosis. Together, these findings suggest that EV-D68 infection is not the sole mediator of neuronal cell death in the spinal cord in those with AFM and that secondary injury from the immune response likely contributes to pathogenesis. IMPORTANCE AFM is a rare condition that causes significant morbidity in affected children, often contributing to life-long sequelae. It is unknown how EV-D68 causes paralysis in children, and effective therapeutic and preventative strategies are not available. Mice are not native hosts for EV-D68, and thus, existing mouse models use immunosuppressed or neonatal mice, mouse-adapted viruses, or intracranial inoculations. To complement existing models, we report two hSCO models for EV-D68 infection. These three-dimensional, multicellular models comprised human cells and include multiple neural lineages, including motor neurons, interneurons, and glial cells. These new hSCO models for EV-D68 infection will contribute to understanding how EV-D68 damages the human spinal cord, which could lead to new therapeutic and prophylactic strategies for this virus.
Topics: Child; Humans; Animals; Mice; Enterovirus D, Human; Spinal Cord; Paralysis; Motor Neurons; Enterovirus Infections
PubMed: 37535397
DOI: 10.1128/mbio.01058-23 -
Biomolecules Oct 2023Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.
Topics: Animals; Humans; Amyotrophic Lateral Sclerosis; Motor Neurons; Muscle, Skeletal; Muscular Atrophy; Paralysis
PubMed: 38002264
DOI: 10.3390/biom13111582 -
Nature Genetics Jul 2023Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is...
Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.
Topics: Animals; Mice; Facial Paralysis; GATA2 Transcription Factor; Motor Neurons; Neurogenesis; Neurons, Efferent
PubMed: 37386251
DOI: 10.1038/s41588-023-01424-9