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Nature Jul 2023Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and...
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.
Topics: Humans; Young Adult; Aging; Brain; Brain Stem; Case-Control Studies; Cognitive Reserve; Disease Progression; Educational Status; Genome-Wide Association Study; Homozygote; Mobility Limitation; Multiple Sclerosis; Protective Factors; Time Factors
PubMed: 37380766
DOI: 10.1038/s41586-023-06250-x -
The Journal of Manual & Manipulative... Dec 2023To determine the long-term clinical effects of spinal manipulative therapy (SMT) or mobilization (MOB) as an adjunct to neurodynamic mobilization (NM) in the management... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To determine the long-term clinical effects of spinal manipulative therapy (SMT) or mobilization (MOB) as an adjunct to neurodynamic mobilization (NM) in the management of individuals with Lumbar Disc Herniation with Radiculopathy (DHR).
DESIGN
Parallel group, single-blind randomized clinical trial.
SETTING
The study was conducted in a governmental tertiary hospital.
PARTICIPANTS
Forty (40) participants diagnosed as having a chronic DHR (≥3 months) were randomly allocated into two groups with 20 participants each in the SMT and MOB groups.
INTERVENTIONS
Participants in the SMT group received high-velocity, low-amplitude manipulation, while those in the MOB group received Mulligans' spinal mobilization with leg movement. Each treatment group also received NM as a co-intervention, administered immediately after the SMT and MOB treatment sessions. Each group received treatment twice a week for 12 weeks.
OUTCOME MEASURES
The following outcomes were measured at baseline, 6, 12, 26, and 52 weeks post-randomization; back pain, leg pain, activity limitation, sciatica bothersomeness, sciatica frequency, functional mobility, quality of life, and global effect. The primary outcomes were pain and activity limitation at 12 weeks post-randomization.
RESULTS
The results indicate that the MOB group improved significantly better than the SMT group in all outcomes ( < 0.05), and at all timelines (6, 12, 26, and 52 weeks post-randomization), except for sensory deficit at 52 weeks, and reflex and motor deficits at 12 and 52 weeks. These improvements were also clinically meaningful for neurodynamic testing and sensory deficits at 12 weeks, back pain intensity at 6 weeks, and for activity limitation, functional mobility, and quality of life outcomes at 6, 12, 26, and 52 weeks of follow-ups. The risk of being improved at 12 weeks post-randomization was 40% lower (RR = 0.6, CI = 0.4 to 0.9, = 0.007) in the SMT group compared to the MOB group.
CONCLUSION
This study found that individuals with DHR demonstrated better improvements when treated with MOB plus NM than when treated with SMT plus NM. These improvements were also clinically meaningful for activity limitation, functional mobility, and quality of life outcomes at long-term follow-up.
TRIAL REGISTRATION
Pan-African Clinical Trial Registry: PACTR201812840142310.
Topics: Humans; Intervertebral Disc Displacement; Radiculopathy; Sciatica; Low Back Pain; Manipulation, Spinal; Quality of Life; Single-Blind Method
PubMed: 36950742
DOI: 10.1080/10669817.2023.2192975 -
Sensors (Basel, Switzerland) Dec 2023Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of... (Review)
Review
Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of cueing through prescribed auditory, visual, and/or tactile cues. Each has shown use to rectify abnormal gait patterns, improving mobility. Yet, a limitation remains, i.e., long-term engagement with cueing modalities. A paradigm shift towards personalised cueing approaches, considering an individual's unique physiological condition, may bring a contemporary approach to ensure longitudinal and continuous engagement. Sonification could be a useful auditory cueing technique when integrated within personalised approaches to gait rehabilitation systems. Previously, sonification demonstrated encouraging results, notably in reducing freezing-of-gait, mitigating spatial variability, and bolstering gait consistency in people with Parkinson's disease (PD). Specifically, sonification through the manipulation of acoustic features paired with the application of advanced audio processing techniques (e.g., time-stretching) enable auditory cueing interventions to be tailored and enhanced. These methods used in conjunction optimize gait characteristics and subsequently improve mobility, enhancing the effectiveness of the intervention. The aim of this narrative review is to further understand and unlock the potential of sonification as a pivotal tool in auditory cueing for gait rehabilitation, while highlighting that continued clinical research is needed to ensure comfort and desirability of use.
Topics: Humans; Quality of Life; Gait; Acoustics; Cues; Parkinson Disease
PubMed: 38202926
DOI: 10.3390/s24010065 -
Brain Communications 2023has been recently reported causing a rare axonal Charcot-Marie-Tooth disease in three independent Caucasian families carrying a recurrent change. We describe the first...
has been recently reported causing a rare axonal Charcot-Marie-Tooth disease in three independent Caucasian families carrying a recurrent change. We describe the first alternative causative mutation in in a family from black African and also observed in a patient of Caucasian ancestry. The disease inheritance was consistent with autosomal dominant and sporadic patterns, respectively. Eight patients and their relatives were enroled from both families. The mean age at diagnosis was 33.9 years, and walking difficulty was commonly the first symptom. Neurological examination showed distal muscle weakness and atrophy, sensory loss and foot and hand deformities. A high clinical variability was noted, but as seen in -associated neuropathy, symptoms were more pronounced in the arms in some patients. Nerve conduction studies showed no response in most of the examined nerves, and an axonal type of neuropathy, where recorded. Whole exome sequencing revealed a novel missense variant (c.1102G>T; Gly368Cys) in , segregating with the disease. Functional analyses showed a significant decrease in CADM3-Gly368Cys protein levels in the membrane and major structural changes in its predicted secondary structure. Therefore, we extend the genotype spectrum of C, underlining the need for genetic studies in underrepresented populations like in Africa.
PubMed: 38074074
DOI: 10.1093/braincomms/fcad227