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Ugeskrift For Laeger Feb 2024Butterfly vertebra anomaly is a rare condition where the vertebral body fails to fuse during embryogenesis. In this case report, we present a 32-year-old male with...
Butterfly vertebra anomaly is a rare condition where the vertebral body fails to fuse during embryogenesis. In this case report, we present a 32-year-old male with progressive lower back pain and paralysis in both lower extremities. CT- and MR-scan showed an isolated L3 butterfly vertebra with a fusion of L2 and L3 discus through the defect and a discus prolapse compressing the spinal canal. The patient underwent successful decompressive surgery and experienced relief in symptoms post-operatively.
Topics: Male; Humans; Adult; Intervertebral Disc Displacement; Low Back Pain; Lower Extremity; Lumbar Vertebrae; Paralysis
PubMed: 38445324
DOI: 10.61409/V09230590 -
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 -
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 -
Anesthesiology Jul 2023The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less... (Clinical Trial)
Clinical Trial
BACKGROUND
The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur.
METHODS
Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h.
RESULTS
Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis.
CONCLUSIONS
When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.
Topics: Humans; Androstanols; Cardiac Surgical Procedures; gamma-Cyclodextrins; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Paralysis; Rocuronium; Sugammadex
PubMed: 37027807
DOI: 10.1097/ALN.0000000000004578 -
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 -
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 -
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 -
Journal of Neurology Sep 2023Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are progressive neurodegenerative syndromes characterised by Parkinsonism with additional features... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are progressive neurodegenerative syndromes characterised by Parkinsonism with additional features including cognitive dysfunction, falls, and oculomotor abnormalities. Understanding the epidemiology of these conditions is critical to planning for future service provision.
METHODS
We conducted a systematic review of studies reporting incidence and prevalence of CBS and PSP. A search of the PubMed and EMBASE data bases was conducted from their date of inception to 13th July 2021. Meta-analysis of studies sharing similar methodologies was carried out to generate estimated pooled prevalence and incidence.
RESULTS
We found 32 studies meeting our criteria for inclusion. There were 20 studies with data on prevalence and 12 with incidence data of PSP. Prevalence of CBS was reported in eight studies while seven studies reported incidence. Reported estimates of prevalence for PSP ranged from 1.00 (0.9-1.1) to 18 (8-28) per 100,000 while prevalence rates for CBS ranged from 0.83 (0.1-3.0) to 25 (0-59). Incidence rates for PSP and CBS respectively ranged from 0.16 (0.07-0.39) to 2.6 per 100,000 person-years and 0.03 (0-0.18) to 0.8 (0.4-1.3) per 100,000 person-years. A random effects model meta-analysis of studies with similar methodologies yielded a pooled prevalence estimate for PSP of 6.92 (4.33-11.06, I = 89%, τ = 0.3907) and 3.91 (2.03-7.51, I = 72%, τ = 0.2573) per 100,000 for CBS.
CONCLUSION
Studies of the epidemiology of PSP and CBS report highly heterogeneous findings. There is a need for further studies using rigorous phenotyping and the most recent diagnostic criteria to understand the true burden of these conditions.
Topics: Humans; Supranuclear Palsy, Progressive; Incidence; Corticobasal Degeneration; Prevalence; Syndrome
PubMed: 37289323
DOI: 10.1007/s00415-023-11791-2 -
Journal of Neurology Nov 2023To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology. (Review)
Review
OBJECTIVE
To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology.
METHODS
Following PRISMA statement recommendations, 338 abstracts were screened independently by two authors. Inclusion criteria were research articles of human patients affected by BFP, either central or peripheral; English, Italian, French or Spanish language; availability of the abstract, while exclusion criteria were topics unrelated to FP, and mention of unilateral or congenital FP. Only full-text articles reporting the diagnostic work-up, the management, and the prognosis of the BFP considered for further specific data analysis.
RESULTS
A total of 143 articles were included, resulting a total of 326 patients with a mean age of 36 years. The most common type of the paralysis was peripheral (91.7%), and the autoimmune disease was the most frequent aetiology (31.3%). The mean time of onset after first symptoms was 12 days and most patients presented with a grade higher than III. Associated symptoms in idiopathic BFP were mostly non-specific. The most frequently positive laboratory exams were cerebrospinal fluid analysis, autoimmune screening and peripheral blood smear, and the most performed imaging was MRI. Most patients (74%) underwent exclusive medical treatment, while a minority were selected for a surgical or combined approach. Finally, in more than half of cases a complete bilateral recovery (60.3%) was achieved.
CONCLUSIONS
BFP is a disabling condition. If a correct diagnosis is formulated, possibilities to recover are elevated and directly correlated to the administration of an adequate treatment.
Topics: Humans; Adult; Facial Paralysis; Facial Nerve Diseases; Causality; Magnetic Resonance Imaging
PubMed: 37523065
DOI: 10.1007/s00415-023-11897-7