Clinical Features, Diagnosis and Treatment Strategies of Limb Girdle Muscular Dystrophy: An Observational Study from South India

Objective: The present observational study describes the natural course of clinical features, family history, and diagnosis pattern and treatment strategies in rare genetic disorder, Limb girdle muscular dystrophy (LGMD). Research Design: Observational study Methods: Clinically/Immunohistochemically/genetically confirmed LGMD patients diagnosed between February 2019 and March 2021 were ambispectively included. The primary outcomes, secondary outcomes such as clinical presentations, behavioral problems, diagnosis pattern and treatment strategies were studied. A correlation of primary outcomes and steroid, non-steroid regimens were achieved. The demographic data was expressed using descriptive statistics mean ± standard deviation [SD]. The significance level was fixed at α = 0.05 Results: 300 LGMD patients were included, out of which 272 patients participated in the study. The mean onset age of symptoms was 8-21 years (13.7 ± 1.9). The mean age of wheelchair bound was found to be between 18 years to 37 years (25.23±1.4) in 123 patients. Bedbound status was attained in 22 patients with a mean age between 18 to 49 years (27.5±2). 7 patients reported death during the study phase with a mean age of 39.2±2.4 (38-45). Comparatively, both steroid and non-steroid regimens using patients exhibited loss of ambulation at 38 years of age. The disease confirmation reported was primarily by clinical examinations (89%) and genetic testing was of minimal number (22%). Conclusion: The outcome measures in the large cohort is similar to that of the Western population despite variability in medical prudence. The contemporary observational study adds to the real-world evidence in approaching better research strategies to treat the LGMD community.

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Limb-girdle Muscular Dystrophy and Therapy: Insights into Cell and Gene-based Approaches

Current Gene Therapy ◽

10.2174/1566523220666200218113526 ◽

2020 ◽

Vol 19 (6) ◽

pp. 386-394

Author(s):

Forough Taheri ◽

Eskandar Taghizadeh ◽

Mohammad J.R. Pour ◽

Daryoush Rostami ◽

Pedram G. Renani ◽

...

Keyword(s):

Muscular Dystrophy ◽

Genome Engineering ◽

Neuromuscular Disorders ◽

Life Quality ◽

Treatment Strategies ◽

Exon Skipping ◽

Gene Replacement ◽

Severe Form ◽

Pharmacological Therapy ◽

Limb Girdle Muscular Dystrophy

The Limb-Girdle Muscular Dystrophies (LGMD) are genetically heterogeneous disorders, responsible for muscle wasting and severe form of dystrophies. Despite the critical developments in the insight and information of pathomechanisms of limb-girdle muscular dystrophy, any definitive treatments do not exist, and current strategies are only based on the improvement of the signs of disorder and to enhance the life quality without resolving an underlying cause. There is a crucial relationship between pharmacological therapy and different consequences; therefore, other treatment strategies will be required. New approaches, such as gene replacement, gene transfer, exon skipping, siRNA knockdown, and anti-myostatin therapy, which can target specific cellular or molecular mechanism of LGMD, could be a promising avenue for the treatment. Recently, genome engineering strategies with a focus on molecular tools such as CRISPR-Cas9 are used to different types of neuromuscular disorders and show the highest potential for clinical translation of these therapies. Thus, recent advancements and challenges in the field will be reviewed in this paper.

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Exercise exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy

10.1101/360388 ◽

2018 ◽

Author(s):

KJ Hughes ◽

A Rodriguez ◽

A Schuler ◽

B Rodemoyer ◽

L Barickman ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Early Onset ◽

Genetic Disorder ◽

Treatment Strategies ◽

Early Death ◽

Initial Assessment ◽

Calcium Dysregulation ◽

C Elegans ◽

Muscle Necrosis

ABSTRACTDuchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and early death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. Thus it remains unresolved if increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle’s disrupted contractile machinery. This knowledge has important applications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1)C. elegansrecapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here we reportdys-1worms display early pathogenesis, including dysregulated sarcoplasmic calcium, and increased lethality. Sarcoplasmic calcium dysregulation indys-1worms precedes overt structural phenotypes (e.g. mitochondrial, and contractile machinery damage) and can be mitigated by silencing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivateddys-1animals in environments requiring high amplitude, or high frequency of muscle exertion during locomotion. We find that several muscular parameters (such as size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of the duration of the effort. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insights into the etiology of the disease, as well as the initial assessment of potential treatment strategies.SIGNIFICANCEDuchenne muscular dystrophy is a degenerative disease affecting tens of thousands of people in the US alone. Much remains unknown about the disease, including the chain of events that links the loss of dystrophin to muscle death, or the extent to which exercise might be able to protect degenerating muscles. We used the nematodeC. elegansto show that sarcoplasmic calcium dysregulation takes place in dystrophic muscles long before other overt signs of damage manifest. When placed in assays that altered muscular activity by increasing either contraction frequency or amplitude, we observed several metrics associated with muscular repair increase. However, no treatment positively affected the life expectancy of dystrophic animals.

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P1.20 Clinical features of limb-girdle muscular dystrophy type 2B with the c.2997G>T mutation

Neuromuscular Disorders ◽

10.1016/j.nmd.2010.07.035 ◽

2010 ◽

Vol 20 (9-10) ◽

pp. 606

Author(s):

T. Takahashi ◽

M. Aoki ◽

N. Suzuki ◽

C. Yaginuma ◽

H. Sato ◽

...

Keyword(s):

Muscular Dystrophy ◽

Clinical Features ◽

Limb Girdle Muscular Dystrophy

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Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2011-301339 ◽

2012 ◽

Vol 84 (4) ◽

pp. 433-440 ◽

Cited By ~ 33

Author(s):

T. Takahashi ◽

M. Aoki ◽

N. Suzuki ◽

M. Tateyama ◽

C. Yaginuma ◽

...

Keyword(s):

Muscular Dystrophy ◽

Clinical Features ◽

Late Onset ◽

Limb Girdle Muscular Dystrophy

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Physical exertion exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1811379116 ◽

2019 ◽

Vol 116 (9) ◽

pp. 3508-3517 ◽

Cited By ~ 6

Author(s):

K. J. Hughes ◽

A. Rodriguez ◽

K. M. Flatt ◽

S. Ray ◽

A. Schuler ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Early Onset ◽

Genetic Disorder ◽

Treatment Strategies ◽

Physical Exertion ◽

Initial Assessment ◽

C Elegans ◽

Muscle Necrosis ◽

Severity Of The Disease

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle’s disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here, we report that dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g., mitochondrial, and contractile machinery damage) and can be mitigated by reducing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high intensity or high frequency of muscle exertion during locomotion. We find that several muscular parameters (e.g., size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of effort duration. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insight into the pathology of the disease as well as the initial assessment of potential treatment strategies.

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P.P.6 08 Clinical features of the limb-girdle muscular dystrophy type 2B

Neuromuscular Disorders ◽

10.1016/j.nmd.2006.05.172 ◽

2006 ◽

Vol 16 (9-10) ◽

pp. 696

Author(s):

T. Takahashi ◽

M. Aoki ◽

H. Aiba ◽

H. Sato ◽

E. Abe ◽

...

Keyword(s):

Muscular Dystrophy ◽

Clinical Features ◽

Limb Girdle Muscular Dystrophy

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Clinical characteristics and surgical outcomes of rhegmatogenous retinal detachment in patients ages 18-40 years

Modern technologies in ophtalmology ◽

10.25276/2312-4911-2021-3-9-14 ◽

2021 ◽

pp. 9-14

Author(s):

T.A. Avanesova ◽

◽

V.V. Anisimova ◽

Keyword(s):

Young Adults ◽

Retinal Detachment ◽

Clinical Features ◽

Surgical Outcomes ◽

Rhegmatogenous Retinal Detachment ◽

Demographic Data ◽

Young Patients ◽

Patients Âgés ◽

The Mean ◽

Anatomic Success

The risk of rhegmatogenous retinal detachment (RRD) increases with age and its more common in the older age group, but several studies report a secondary peak of RRD in young patients. At the same time, RRD in young patients has clinical features. Purpose. To describe clinical features and surgical outcomes of RRD in young adults. Materials and мethods. Retrospective study of 33 patients (33 eyes) aged between 18 and 40 years, who underwent primary surgery between June 2018 and February 2021. The mean age of the patients was 33.9±6.7 years. All patients underwent either scleral buckling or pars plana vitrectomy. We analyzed demographic data, RRD characteristics, primary and final anatomic anatomic success rate and best-corrected visual acuity (BCVA) at the conclusion of follow-up. Results. The main etiologies were myopia (87.8%) and trauma (15%). were Macula on RRD was in 69.7% of patients. Primary anatomic success was in 69.7% cases, final anatomic success- 94%. (14 out of 16 eyes) after vitrectomy. The mean BCVA value improved to 0.65±0.35 (p=0.042). Conclusion. RRD in young adults aged between 18 and 40 years has clinical features and differs from that in older adults. The main causes are myopia, especially of high myopia and trauma. Macula off RRD is less common than macula on RRD. Primary anatomic success is less favorable compared to final anatomic success. The functional prognosis remains satisfactory and increased to 0.65±0.35 (p=0.042).

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Cluster headache beyond the pain phase

Neurology ◽

10.1212/01.wnl.0000542491.92981.03 ◽

2018 ◽

Vol 91 (9) ◽

pp. e822-e831 ◽

Cited By ~ 8

Author(s):

Agneta Snoer ◽

Nunu Lund ◽

Rasmus Beske ◽

Andreas Hagedorn ◽

Rigmor Højland Jensen ◽

...

Keyword(s):

Observational Study ◽

Cluster Headache ◽

Clinical Features ◽

Prospective Observational Study ◽

Treatment Strategies ◽

Duration Of Symptoms ◽

Autonomic Symptoms ◽

Mood Changes ◽

Abortive Treatment ◽

The Given

ObjectiveTo describe the nature, prevalence, and duration of symptoms in the preictal, ictal, and postictal phases of cluster headache (CH) attacks.MethodsFifty-seven patients with episodic or chronic CH participated in this prospective, observational study. In a questionnaire concerning 33 CH and migraine-related symptoms, patients reported the clinical features of up to 10 CH attacks/patient. The questionnaire was divided into 3 sections: a preictal phase, ictal phase, and postictal phase. For each phase, patients documented whether the given symptom was present, and if possible estimated the duration of the symptom.ResultsIn total, 500 CH attack descriptions were obtained. In the preictal phase, general symptoms (most frequently concentration difficulties, restlessness, and mood changes) occurred 20 minutes prior to 46.0% of attacks. Local painful and autonomic symptoms were observed 10 minutes prior to 54.6% and 35% of attacks, respectively. Postictally, pain and autonomic symptoms resolved over 20 minutes, leaving patients with fatigue (36.2%), decreased energy (39.0%), and concentration difficulties (27.6%), lasting a median of 60 minutes.ConclusionsPreictal and postictal symptoms are very frequent in CH, demonstrating that CH attacks are not composed of a pain phase alone. Since the origin of CH attacks is unresolved, studies of preictal and postictal symptoms could contribute to the understanding of CH pathophysiology and, potentially, early, abortive treatment strategies.

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