Neuroanatomical Models of Muscle Strength and Relationship to Ambulatory Function in Spinal Muscular Atrophy

2020 ◽  
Vol 7 (4) ◽  
pp. 459-466
Author(s):  
Rafael Rodriguez-Torres ◽  
Julia Fabiano ◽  
Ashley Goodwin ◽  
Ashwini K. Rao ◽  
Stacy Kinirons ◽  
...  

Background: Individuals with spinal muscular atrophy (SMA) III walk independently, but experience muscle weakness, gait impairments, and fatigue. Although SMA affects proximal more than distal muscles, the characteristic pattern of selective muscle weakness has not been explained. Two theories have been proposed: 1) location of spinal motor neurons; and 2) differences in segmental innervation. Objective: To identify neuroanatomical models that explain the selective muscle weakness in individuals with SMA and assess the relationship of these models to ambulatory function. Methods: Data from 23 ambulatory SMA participants (78.2% male), ages 10–56 years, enrolled in two clinical studies (NCT01166022, NCT02895789) were included. Strength was assessed using the Medical Research Council (MRC) score; ambulatory function was measured by distance walked on the 6-minute walk test (6 MWT). Three models were identified, and relationships assessed using Pearson correlation coefficients and linear regression. Results: All models demonstrated a positive association between strength and function, (p < 0.02). Linear regression revealed that Model 3B, consisting of muscles innervated by lower lumbar and sacral segments, explained 67% of the variability observed in 6 MWT performance (β= 0.670, p = 0.003). Conclusions: Muscles innervated by lower lumbar and sacral segments, i.e. hip extensors, hip abductors, knee flexors and ankle dorsiflexors, correlated with and predicted greater ambulatory function. The neuroanatomical patterns of muscle weakness may contribute to a better understanding of disease mechanisms and enable delivery of targeted therapies.

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Xiu-Fen Liu ◽  
Dong-Xin Wang ◽  
Daqing Ma

Spinal muscular atrophy (SMA) is a rare genetic disease characterized by degeneration of spinal cord motor neurons, which results in hypotonia and muscle weakness. Patients with type IV SMA often have onset of weakness from adulthood. Anesthetic management is often difficult in these patients as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents as shown by (Lunn and Wang; 2008, Simic; 2008, and Cifuentes-Diaz et al.; 2002). Herein we report a case of anesthetic management of a patient with SMA type IV for mammectomy and review some other cases of SMA patients receiving different kinds of anesthesia.


2021 ◽  
Vol 9 (11) ◽  
pp. 2897-2902
Author(s):  
Raheena B ◽  
Shaila Borannavar ◽  
Ananta S Desai

Spinal Muscular Atrophy (SMA) is the second leading genetic disorder inherited in the autosomal recessive pattern due to the absence of the SMN1 gene characterized by loss of motor neurons and progressive muscle wasting, often leading to dependent life and decreased life span. In Ayurveda, this condition can be considered as Kulaja Vyadhi wherein the patient’s Mamsa and Snayu is affected by Vata. This can be regarded as Mamsa-Snayugata Sarvanga Vata. It is said that Prakruta Vata dosha is the life, it is the strength, it is the sustainer of the body, it holds the body and life together. If it is Vikruta it produces Sankocha, Khanja, Kubjatva, Pangutva, Khalli and Soshana of Anga. So, in this disease aggravated Vata does the vitiation of Mamsa and Snayu thus leading to Soshana of both, resulting in Stambha, Nischalikarana of Avayava. A 21years female patient was admitted to our I.P.D with c/o of reduced strength in all four limbs leading to the inability to walk and to maintain erect posture during standing and sitting positions. Based on Ayurvedic principles the patient was initially subjected to Avaranahara Chikitsa followed by Brimhana line of management. Keywords: Mamsagata vata, Snayugata vata, Sarvanga vata, Spinal muscular atrophy (SMA)


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tai-Heng Chen ◽  
Jun-An Chen

Two crucial questions in neuroscience are how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable to neurodegenerative diseases. In the central nervous system, spinal motor neurons serve as one of the best-characterized cell types for addressing these two questions. In this review, we dissect these questions by evaluating the emerging role of regulatory microRNAs in motor neuron generation in developing embryos and their potential contributions to neurodegenerative diseases such as spinal muscular atrophy (SMA). Given recent promising results from novel microRNA-based medicines, we discuss the potential applications of microRNAs for clinical assessments of SMA disease progression and treatment.


2019 ◽  
Vol 7 (7) ◽  
pp. 2327-2335
Author(s):  
Nadia Mazzarella ◽  
Ivana Giangrieco ◽  
Serena Visone ◽  
Pamela Santonicola ◽  
Jannis Achenbach ◽  
...  

2020 ◽  
Vol 24 (5) ◽  
pp. 457-460
Author(s):  
Lauren A.V. Orenstein ◽  
Adaugo Amah ◽  
Fiona M. Shaw ◽  
Chao Zhang ◽  
Robert A. Swerlick ◽  
...  

Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that severely impairs patients’ quality of life (QoL). Instruments such as the 10-item Dermatology Life Quality Index and 16-item Skindex-16 have been used to assess QoL in HS; however, it is unknown whether the shorter 3-item Skindex-mini can also provide an accurate assessment of skin-related QoL in patients with HS. Objectives The aim was to assess how well the Skindex-16 correlates with its shorter adaptation, the Skindex-mini, in capturing QoL among patients with HS. Methods This retrospective cross-sectional study included all HS patients seen in the HS Clinic at The Emory Clinic between January 1, 2019, and August 16, 2019. We compared the correlation between the symptom, emotion, and function domains of the Skindex-16 and Skindex-mini using Pearson correlation coefficients (CC). Secondary outcome measures included individual survey item analysis, ItchyQuant scores, and numeric rating scale of pain. Results We identified 108 encounters among 75 unique hidradenitis suppurativa patients (43 black/African American, 18 white, 5 Asian/Pacific Islander, 3 Latino, 4 Other, 2 unknown). Pearson CC between the Skindex-16 and Skindex-mini domain scores for all encounters were 0.770 ( P < .001), 0.787 ( P < .001), and 0.801 ( P < .001) for the symptom, emotion, and function domains, respectively. The mean pain and ItchyQuant scores were 4.14 (SD 3.31) and 3.55 (SD 3.34), respectively. Conclusions The Skindex-mini correlated highly with the Skindex-16 in a racially diverse group of patients with HS. The Skindex-mini is a streamlined QoL instrument that could be practically implemented into routine clinical care among diverse patients presenting to dermatology.


2016 ◽  
Vol 10 ◽  
pp. JEN.S33122 ◽  
Author(s):  
Saif Ahmad ◽  
Kanchan Bhatia ◽  
Annapoorna Kannan ◽  
Laxman Gangwani

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1) gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a) regulation of SMN gene expression and (b) degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA.


2011 ◽  
Vol 32 (1) ◽  
pp. 126-138 ◽  
Author(s):  
M. Ruggiu ◽  
V. L. McGovern ◽  
F. Lotti ◽  
L. Saieva ◽  
D. K. Li ◽  
...  

2005 ◽  
Vol 25 (13) ◽  
pp. 5543-5551 ◽  
Author(s):  
Lili Wan ◽  
Daniel J. Battle ◽  
Jeongsik Yong ◽  
Amelie K. Gubitz ◽  
Stephen J. Kolb ◽  
...  

ABSTRACT Reduction of the survival of motor neurons (SMN) protein levels causes the motor neuron degenerative disease spinal muscular atrophy, the severity of which correlates with the extent of reduction in SMN. SMN, together with Gemins 2 to 7, forms a complex that functions in the assembly of small nuclear ribonucleoprotein particles (snRNPs). Complete depletion of the SMN complex from cell extracts abolishes snRNP assembly, the formation of heptameric Sm cores on snRNAs. However, what effect, if any, reduction of SMN protein levels, as occurs in spinal muscular atrophy patients, has on the capacity of cells to produce snRNPs is not known. To address this, we developed a sensitive and quantitative assay for snRNP assembly, the formation of high-salt- and heparin-resistant stable Sm cores, that is strictly dependent on the SMN complex. We show that the extent of Sm core assembly is directly proportional to the amount of SMN protein in cell extracts. Consistent with this, pulse-labeling experiments demonstrate a significant reduction in the rate of snRNP biogenesis in low-SMN cells. Furthermore, extracts of cells from spinal muscular atrophy patients have a lower capacity for snRNP assembly that corresponds directly to the reduced amount of SMN. Thus, SMN determines the capacity for snRNP biogenesis, and our findings provide evidence for a measurable deficiency in a biochemical activity in cells from patients with spinal muscular atrophy.


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