Muscle Weakness Research Articles

Clinical Characteristics of Anti-Synthetase Syndrome: Analysis from the CLASS project.

Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD. We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort. Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD. We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD.

THE EFFECT OF A MODIFIED TENODESIS WRIST-HAND ORTHOSIS ON HAND FUNCTION IN PATIENTS WITH TETRAPLEGIA

BACKGROUND: An individual experiencing tetraplegia faces functional limitations due to impaired hand function. The use of an affordable tenodesis wrist-hand orthosis (WHO) can enable finger flexion with active wrist extension, thereby enhancing the three-jaw chuck grasp and overall hand functionality. OBJECTIVES: To assess hand function and satisfaction in patients with tetraplegia using a modified tenodesis wrist-hand orthosis (WHO), utilizing the Duruöz Hand Index (DHI) and the Orthotics and Prosthetics User Survey (OPUS) satisfaction with device and services subscales. METHODOLOGY: The study was conducted at a tertiary care center in central India, enrolling patients with tetraplegia admitted to the Department of Physical Medicine and Rehabilitation. A modified tenodesis wrist-hand orthosis (WHO) was designed using low-temperature thermoplastic components. Twenty-two individuals with a minimum wrist extensor power of grade 3/5 were included in the study. These patients were provided with the modified tenodesis WHO and underwent daily training sessions for a period of 2 weeks. Duruöz Hand Index (DHI) scores were assessed at baseline, 6 weeks, and 12 weeks post-enrolment. Patient satisfaction was evaluated using the Orthotics and Prosthetics User’s Survey (OPUS) satisfaction with device and services subscales. FINDINGS: The analysis of the DHI scores indicated a significant enhancement in functional abilities at both 6-week and 12-week follow-ups compared to the baseline assessment. Notably, the most substantial progress at 6 weeks follow-up was observed in tasks such as buttoning a shirt, while significant improvement at the 12-week mark was noted in activities like turning a key in a lock. The median OPUS device satisfaction score was 50, corresponding to a Rasch score of 68.8. Additionally, the median OPUS satisfaction score for services stood at 46, with a Rasch score of 72.7. Patients expressed the highest satisfaction levels with the courteous demeanor of the staff, prompt scheduling of appointments, and accurate fitting of the orthosis. CONCLUSION: The study findings indicate that the modified tenodesis WHO is an effective and satisfactory therapeutic device for improving hand function in patients with tetraplegia. The findings encourage further investigation and application of the modified tenodesis WHO in clinical practice. Layman's Abstract Individuals who are affected due to spinal cord injury (SCI) are often unable to perform the basic daily activities of life due to weakness. The hands are one of the most specialized parts of the human body and loss of its function can be incapacitating. Certain wrist hand orthoses (WHO) can aid such individuals by assisting the weak hand muscles. One such WHO is a tenodesis wrist hand orthosis. Modifications to the previously available tenodesis wrist hand orthosis were made to make it cheaper, lighter, and easier to manufacture. The effectiveness of this modified tenodesis WHO on improving hand activity and satisfaction in the individuals using it was assessed in this study which was conducted in a tertiary care center in central India. Twenty-two individuals with cervical SCI, who had some ability to extend their wrists against gravity, were admitted to the Physical Medicine and Rehabilitation department and enrolled in this study. Notable improvements were observed in functional tasks such as buttoning a shirt, opening a lock, eating with a fork, brushing teeth, and writing, with considerable satisfaction in those trained with the modified tenodesis WHO. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/42879/33253 How To Cite: Sonune S.P, Saha A, Joshi N.G, Pathak S, Bhadra P, Goel G. The effect of a modified tenodesis wrist-hand orthosis on hand function in patients with tetraplegia. Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 1, No.8. https://doi.org/10.33137/cpoj.v7i1.42879 Corresponding Author: Dr. Anyesha Saha,Affiliation: Department of Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, Saket Nagar, Bhopal (M.P.), India.E-Mails: saha.anyesha@gmail.com; anyesha.sr2023@aiimsbhopal.edu.inORCID ID: https://orcid.org/0009-0004-1574-0519

Genotype‒phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.

Intramyocardial fatty infiltration lesion in sporadic inclusion body myositis: a case report.

Sporadic inclusion body myositis (sIBM), the most common inflammatory muscle disorder in adults over 50 years, is often misdiagnosed due to its gradual onset and its common but unspecific muscle weakness in older adults. Diagnosis relies on clinical, radiological, and pathological features. Cardiac involvement is rare, prompting this case description and a comprehensive literature analysis. A 73-year-old woman diagnosed with sIBM in 2021 through muscle biopsy had been experiencing muscular symptoms since 2015. Her condition progressively worsened, affecting daily activities. Annual follow-ups revealed a moderate obstructive syndrome on respiratory testing, prompting a cardiac evaluation. Cardiac magnetic resonance (CMR) imaging identified intramyocardial lesions consistent with fatty infiltration, highlighting the interest of advanced imaging in sIBM management. Cardiac involvement in sIBM is presumed rare compared to other idiopathic inflammatory myopathies, though the exact frequency remains unclear. Early identification of heart alterations by CMR in sIBM can be prognostically valuable, guiding follow-up and interventions. However, literature on this subject is limited to small cohort studies and case reports describing complications. Given the slow progression of sIBM and the limited efficacy of current treatments, the discovery of myocardial lesions could warrant closer cardiological monitoring. Larger cohort studies are needed to explore potential new therapeutic approaches. Our case underscores the importance of CMR in detecting subtle cardiac manifestations in sIBM and illustrates the potential prognostic value of cardiac assessment in the management of sIBM.

Clinical characteristics of idiopathic inflammatory myopathies related to anti-SRP: a single center experience

Idiopathic inflammatory myopathy (IIM) with autoantibodies recognizing the signal recognition particle (SRP) is characterized by prominent proximal weakness, infrequent extramuscular involvement, dramatically elevated creatine kinase levels, and myofiber necrosis with few inflammatory cell infiltrates in muscle tissue. To enhance understanding of the clinically used diagnosis and treatment of this disease, this study presents a single-center experience and analysis of a Chinese cohort with anti-SRP IIM. The most recent European Neuromuscular Center criteria were used to include Anti-SRP IIM patients from September 2016 to November 2019. Prior to treatment initiation, all sera were collected for the detection of anti-SRP autoantibodies and other myositis-related autoantibodies. Muscle strength, concurrent autoimmune conditions, comorbidities like interstitial lung disease (ILD), treatment outcomes, and follow-up results were also documented. Univariate logistic regression was employed to determine factors affecting prognosis. Among 271 patients with IIM, we identified 23 (8.5%) patients with anti-SRP IIM. Lower limb muscle weakness was frequently more severe. Interstitial lung disease (ILD) was observed in 50% of anti-SRP IIM patients. The presence of ILD may serve as a predictor of a poor prognosis, as revealed by univariate logistic regression analysis (odds ratio, 3.8, 95% CI: 1.0-6.8, p = 0.05).This Chinese Anti-SRP IIM cohort from Hunan province seems to have higher incidences of ILD, and associated ILD may be a risk factor for a poor prognosis. To fully understand the specific role of the anti-SRP autoantibody in this unique subset with ILD, further research is necessary.

Approaches to Managing Herniated Disc Surgical vs. Conservative Treatment

Introduction Disc herniation is a displacement of an intervertebral disc, most often caused by degeneration of its outer layer, the annulus fibrosus. This condition can cause various symptoms such as numbness, pain, muscle weakness or lose of sensation. While many patients can be successfully treated with non-surgical methods, some of them some require surgical intervention. Aim of study The objective of this study is to evaluate both surgical and non-surgical treatment methods for herniated disc and seeks to introduce doctors and patients to the advantages and disadvantages associated with them. State of Knowledge Disk herniation occurs when disk material prolapses beyond intervertebral disk’s space. The symptoms may arise when displaced material start to compress major structures located nearby, such as spinal nerves. The most common causes include age-related degeneration, repetitive movements, obesity, trauma or genetic predisposition. Summary (Conclusion) Disk herniation can be managed with various non-surgical and surgical methods. Conservative treatment should be considered as first line treatment showing high success rate for mild to moderate cases in long term relief and preventing recurrence of symptoms. Surgical options offer better short-term relief for sever and more advanced cases but carry greater risks of side effects and involve longer recovery time. Best approach should be carefully selected based on the severity of symptoms and patient needs.

Feasibility of a new bicycle ergometer with adjustable pedaling configuration for personalized lower limb rehabilitation

Muscle atrophy due to prolonged immobilization leads to severe dysfunction and progression of disease and injury. This highlights the necessity for early rehabilitation, even during the non-ambulatory stages. As manifestations vary among individuals, target-specific rehabilitation is crucial for achieving optimal outcomes. Conventional bicycle ergometers, despite their wide usage in rehabilitation and sports training, fail to adequately recruit the muscles that predominantly operate in the coronal or axial plane. This is thought to be due to the restriction of pedaling trajectory in the sagittal plane. This study introduces a new bicycle ergometer capable of tilting the pedaling plane and adjusting the pedal orientation, in order to alter muscle recruitment patterns and limb alignments. A biomechanical analysis of eight healthy volunteers suggests that our device can elicit dynamic valgus/varus alignment and alter the axial rotations of the lower extremities. An electromyography analysis revealed a significant increase in the activation of specific muscle groups, particularly the abductors and adductors, suggesting promising results for targeted muscle recruitment. We expect this ergometer to provide a new method for target-specific rehabilitation and the treatment of bedridden patients or those with weak muscles.

Anti-SRP Antibodies and Myocarditis in Systemic Sclerosis Overlap Syndrome with Immune-Mediated Necrotizing Myositis (IMNM)

Overlap syndrome of systemic sclerosis and idiopathic inflammatory myopathies is an increasingly frequent entity, but the association with immune-mediated necrotizing myositis has rarely been described. While myositis or myopathy may be features of scleroderma, it is imperative to correctly diagnose an overlap syndrome of these two, since it can be considered a different entity with specific management and a worse prognosis. Anti-signal recognition particle (anti-SRP) antibodies target the striated muscle fiber and inhibit myoblast regeneration, resulting in myofiber atrophy and necrosis. Anti-SRP antibodies are specific in immune-mediated necrotizing myopathy characterized by myonecrosis and minimal inflammatory reaction, with proximal muscle weakness and typical extra-muscular manifestation. There are controversial data on the association of cardiac manifestations and the presence of these antibodies, and recent studies cannot prove a significant correlation between the two. Myocarditis is a complication with an unpredictable, potentially severe outcome from heart failure and dilated cardiomyopathy to fatality. It can be difficult to diagnose, and a myocardial biopsy can be problematic in daily practice; thus, most practitioners rely on cardiac magnetic resonance with suggestive images for the correct diagnosis. This paper seeks to address the challenges associated with the diagnosis and treatment of collagen diseases by evaluating the role of anti-SRP antibodies in the pathogenesis of cardiac involvement.

Mitochondrial-targeted plastoquinone therapy ameliorates early onset muscle weakness that precedes ovarian cancer cachexia in mice.

Cancer cachexia, and the related loss of muscle and strength, worsens quality of life and lowers overall survival. Recently, a novel 'pre-atrophy' muscle weakness was identified during early-stage cancer. While mitochondrial stress responses are associated with early-stage pre-atrophy weakness, a causal relationship has not been established. Using a robust mouse model of metastatic epithelial ovarian cancer (EOC)-induced cachexia, we found the well-established mitochondrial-targeted plastoquinone SkQ1 partially prevents pre-atrophy weakness in the diaphragm. Furthermore, SkQ1 improved force production during atrophy without preventing atrophy itself in the tibialis anterior and diaphragm. EOC reduced flexor digitorum brevis (FDB) force production and myoplasmic free calcium ([Ca 2+ ] i ) during contraction in single muscle fibers, both of which were prevented by SkQ1. Remarkably, changes in mitochondrial reactive oxygen species and pyruvate metabolism were heterogeneous across time and between muscle types which highlights a considerable complexity in the relationships between mitochondria and muscle remodeling throughout EOC. These discoveries identify that muscle weakness can occur independent of atrophy throughout EOC in a manner that is linked to improved calcium handling. The findings also demonstrate that mitochondrial-targeted therapies exert a robust effect in preserving muscle force during the early pre-atrophy period and in late-stage EOC once cachexia has become severe.

Comparison of the long-term efficacy of ROI-C and conventional cage-plate in treatment of spinal cord injury without fracture or dislocation: a retrospective study

BackgroundThe self-locking cage (ROI-C, LDR, Troyes, France) has been clinically applied in the treatment of cervical degenerative disc disease (CDDD). However, only a few long-term clinical and radiographic studies have been conducted on the treatment of spinal cord injury without fracture or dislocation (SCIWFD) so far. A comparison between ACDF with either ROI-C or CCP was performed to determine the better treatment for SCIWFD.MethodsA total of 83 patients who underwent ACDF using either ROI-C or CCP were reviewed for radiological and clinical outcomes. The cohort comprised 60 males and 23 females, aged between 32 and 88 years old, with an average age of 58.23 years. All patients exhibited symptoms of nerve injury, including limb numbness, muscle weakness, hypoesthesia or urinary dysfunction. The preoperative ASIA classification of spinal nerve function: 7 cases of grade A, 23 cases of grade B, 34 cases of grade C and 19 cases of grade D were included in the study.ResultsA total of 48 patients underwent ACDF with ROI-C, while 35 patients received a conventional cage-plate. They were studied with a follow-up of 28.63 ± 17.41 months and 29.48 ± 15.43 months respectively. No significant difference was found in blood loss, JOA and ASIA between the two groups. No significant difference was found in cervical lordosis (CL) (P > 0.05). However, statistical difference was found in disc height of fused segment and T1 slope between the two groups (P < 0.05). No statistical difference was in the incidence of cage subsidence (P > 0.05). There was significant difference in the incidence of dysphagia. Both of two groups achieved bony fusion at final follow-up.ConclusionOur study demonstrated that ROI-C has the same efficacy as CCP in improving the cervical stability in treatment of SCIWFD. The migration of cage didn’t occur in ROI-C group at final follow-up, showing steadily fixed in cervical column. Moreover, the ROI-C does have the advantages of good therapeutic effect, mis-invasive, shorter operation time and fewer complications.

Whole milk protein powder separated by low-temperature nanofiltration membrane administration alleviates sepsis-induced myopathy

Sepsis-induced myopathy (SIM) has been recognized as a critical risk factor for the development of acquired muscle weakness among patients in the intensive care unit. These individuals frequently encounter inadequate dietary intake and malnutrition. With the aggravation of the severity of the person’s condition, leading to increased skeletal muscle protein breakdown and reduced synthesis, which is an urgent problem to be solved in clinical nutritional treatment. Whole milk protein powder (WMPP) has promising bioactive nutrients and holds promising potential for enhancing skeletal muscle mass. The study was designed to delve into the potential effects and mechanisms of WMPP intervention for increaseing skeletal muscle mass on SIM mice. Our results clearly show that the intervention with WMPP can significantly improve the exercise capacity and skeletal muscle mass in SIM mice. It significantly increases the diameter and cross-sectional area (CSA) of skeletal muscle fibers, while effectively reducing the excessive aggregation of collagen fibers and the abnormal accumulation of adipose tissue in the skeletal muscle of SIM mice. Moreover, WMPP intervention also significantly alleviated the oxidative stress status of mitochondria, which subsequently enhanced the expression of mitochondrial metabolic enzymes. The mechanism may be associated with decreased AMPK phosphorylation in skeletal muscle tissue and simultaneously increased phosphorylation of mTOR, p70S6K1, and 4EBP-1 in SIM mice. In summary, the WMPP intervention significantly enhances exercise capacity and skeletal muscle mass while mitigating the oxidative stress status of mitochondria. Furthermore, it regulates skeletal muscle anabolism via the AMPK/mTOR signaling pathway in SIM mice.

Effect of Ankle Foot Orthosis (AFO) on kinematics in Children with Cerebral Palsy (CP)

Introduction: Children with cerebral palsy have impaired motor control, caused by prenatal and postnatal causes that affect the developing brain which leads to Muscle weakness, sensory loss, and stiffness Objective: To assess the efficacy of floor reaction orthoses (FRO) and solid ankle foot orthoses (AFO) with gait's temporospatial factors. Methodology: It was experimental based with custom molded Floor reaction orthosis and Solid ankle foot orthosis, the sampling technique was Non-probability Convenience sampling the targeted population was CP patients, and trials were taken from the patient. Results: FRAFO significantly improved patient cadence, velocity, stride time, stance, and swing phases compared to SAFO, with better improvement in kinetic dynamics and a decrease in stance and swing phases. Conclusion: FRAFO is more effective than SAFO.

The association of early passive mobilization with intracranial pressure in the adult intensive care unit: A prospective, cohort study.

Early mobilization are key components of the ABCDEF Care Bundle and critical treatments to reduce acquired muscle weakness, delirium and prolonged intensive care unit (ICU) stay. This study aimed to determine whether routine early mobilization related to intracranial pressure in intensive care patients on mechanical ventilation, using optic nerve sheath diameter measurement (ONSD). This study was planned as a prospective, cohort study in the third-step adult ICU of a faculty hospital. The study included only patients who were intubated and followed up on a mechanical ventilator and were clinically stable. Passive range of motion (PROM) exercises were performed daily by the physiotherapists as part of routine care from the day of hospitalization. ONSD was assessed before, during and 10 min after PROM exercises. The study included 20 eligible patients out of the 142 who were evaluated upon admission to the ICU. The median age of the patients was 65 years, and nine (45%) of them were female. The analyses showed that there was no statistically significant change in ONSD during and at the end of the PROM (ONSD right eye p:.621, Partial η2: 0.025, ONSD left eye p:.935, Partial η2: 0.004). Similarly, there was no statistically significant change in haemodynamic parameters in during and at the end of the PROM (Heart beat p:.849, Partial η2: 0.009, Systolic Pressure p:.435, Partial η2: 0.043, Diastolic Pressure p:.128, Partial η2:0.103, Saturation p:.103, Partial η2: 0.113 and Respiratory rate p:.071, Partial η2:0.130). This study suggests that daily extremity physiotherapy exercises can be safely applied without causing increased intracranial pressure or haemodynamic instability in intensive care patients followed up on mechanical ventilation, including patients with vasopressor therapy. Early mobilization, including PROM, is considered safe in terms of intracranial pressure for intubated patients in the ICU.

Risk factors affecting cervical spondylotic myelopathy complicated with traumatic central cord syndrome and the efficacy of different treatment options

ObjectiveTo analyze the influencing factors and treatment options of cervical spondylotic myelopathy (CSM) complicated with traumatic central cord syndrome (TCCS).MethodsA total of 243 patients with CSM admitted to our hospital from January 2021 to September 2022 were retrospectively analyzed, and then divided into the control group (n = 152) and the observation group (n = 91) according to the presence or absence of concurrent TCCS. The clinical data and imaging data of the two groups were compared, and multivariate logistic regression was used to analyze the influencing factors of CSM complicated with TCCS. Patients in the observation group were further divided into the zero notch anterior cervical interbody fusion device (Zero-P) group (n = 45) and the cervical spine locking plate (CSLP) group (n = 46) according to the treatment mode, and the perioperative indexes of the two groups were compared. The treatment effects were evaluated by the American Spinal Injury Association (ASIA) and the Japanese Orthopedic Association (JOA) before surgery, 1 week after surgery and 6 months after surgery. The height of intervertebral space and the cervical lordosis angle were measured.ResultsMultivariate logistic regression analysis showed that the injury mechanism (hyperextension injury), hand muscle weakness, cervical instability, age, degree of cervical spinal stenosis, degree of cervical spinal cord compression, and changes in intramedullary high signal were the risk factors, while the type of compression (soft), ASIA score and JOA score were the protective factor for CSM complicated with TCCS (P < 0.05). Patients in Zero-P group had much shorter operation time and hospitalization time than these in CSLP group (P < 0.05). The cervical lordosis angle and intervertebral space height at 1 week and 6 months after operation in the two groups were both largely higher than these before operation, and the cervical lordosis angle and intervertebral space height in the Zero-P group were significantly higher than these in the CSLP group one week after surgery (P < 0.05). The ASIA score and JOA score were obviously increased in the two groups 1 week and 6 months after surgery, and the ASIA score and JOA score in the Zero-P group were significantly higher than these in the CSLP group at 1 week after surgery (P < 0.05).ConclusionThe mechanism of TCCS in CSM is still controversial, which it is generally believed to be caused by cervical hyperextension injury. The clinical symptoms are diverse, and the treatment methods are also different. This study shows that the mechanism of injury, type of compression, hand muscle weakness, cervical instability, age, cervical stenosis compression, and intramedullary high signal changes are all risk factors for CSM complicated with TCCS. Early identification of risk factors and targeted interventions can effectively reduce the complicated rate of TCCS. Zero-P and CSLP surgical fixation have good efficacy in the treatment of TCCS, and there is little difference in efficacy between the two. However, Zero-P fixation surgery has the advantages of short operation time and fast postoperative recovery.

Compound Heterozygous Loss of Allele Coding for KCNJ16 in an Adult Presenting as Recurrent Hypokalemic Periodic Paralysis with Metabolic Acidosis and Hypokalemia

A 20-year-old male presented with fever and rapidly progressive muscle weakness. He had hypokalemia and metabolic acidosis, suggesting renal tubular acidosis (RTA). Further investigation revealed distal RTA with preserved acidification. A channelopathy was suspected. Whole exome sequencing identified a novel biallelic mutation in the KCNJ16 gene, which encodes the Kir5.1 protein. This is the first reported case of an Indian adult with biallelic KCNJ16 mutations presenting as pure renal phenotype without sensory neural hearing loss or cardiac manifestation.

Alzheimer’s Disease: Understanding Motor Impairments

Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder and the leading cause of dementia worldwide, profoundly impacts health and quality of life. While cognitive impairments—such as memory loss, attention deficits, and disorientation—predominate in AD, motor symptoms, though common, remain underexplored. These motor symptoms, including gait disturbances, reduced cardiorespiratory fitness, muscle weakness, sarcopenia, and impaired balance, are often associated with advanced stages of AD and contribute to increased mortality. Emerging evidence, however, suggests that motor symptoms may be present in earlier stages and can serve as predictive markers for AD in older adults. Despite a limited understanding of the underlying mechanisms driving these motor symptoms, several key pathways have been identified, offering avenues for further investigation. This review provides an in-depth analysis of motor symptoms in AD, discussing its progression, potential mechanisms, and therapeutic strategies. Addressing motor symptoms alongside cognitive decline may enhance patient functionality, improve quality of life, and support more comprehensive disease management strategies.

MicroRNAs as Biomarkers in Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA. Currently, there is a lack of reliable biomarkers to monitor SMA; therefore, the search for novel SMA biomarkers, including miRNAs, is crucial as reliable tools are needed to track disease progression, predict the response to therapy and understand the different clinical outcomes of available treatments. In this review, we compile data on miRNAs associated with SMA pathogenesis and their potential use as biomarkers. Based on current knowledge, the most frequently deregulated miRNAs between SMA patients and controls, as well as pre- and post-treatment in SMA patients, include miR-1-3p, miR-133a-3p, miR-133b, and miR-206. These findings offer promising possibilities for improving patient classification and monitoring disease progression and response to treatment. Additionally, these findings provide insights into the broader molecular mechanisms and networks of SMA that could inform the development of future therapeutic strategies.

A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study

BackgroundSELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.5-year natural history follow-up showed that 90% of the patients had low bone quality, respiratory impairments were found in all SELENON-RM and most of the LAMA2-MD patients, and many had cardiac risk factors. However, further extensive knowledge on long-term natural history data, and clinical and functional outcome measures is needed to reach trial readiness. Therefore, we extended the natural history study with 3- and 5-year follow-up visits (Extended LAST STRONG).MethodsThe Extended LAST STRONG is a long-term natural history study in Dutch-speaking patients of all ages diagnosed with genetically confirmed SELENON-RM or LAMA2-MD, starting in September 2023. Patients visit our hospital twice over a period of 2 years to complete a 5-year follow up from the initial LAST-STRONG study. At both visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, muscle ultrasound, respiratory assessments (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), Dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years), X-ray of the left hand (age ≤ 17 years), lower extremity MRI (age ≥ 10 years), accelerometry for 8 days (age ≥ 2 years), and questionnaires (patient report and/or parent proxy; age ≥ 2 years). All examinations are adapted to the patient’s age and functional abilities. Disease progression between all subsequent visits and relationships between outcome measures will be assessed.DiscussionThis study will provide valuable insights into the 5-year natural history of patients with SELENON-RM and LAMA2-MD and contribute to further selecting relevant and sensitive to change clinical and functional outcome measures. Furthermore, this data will help optimize natural history data collection in clinical care and help develop clinical care guidelines.Trial registrationThis study protocol including the patient information and consent forms has been approved by medical ethical reviewing committee (‘METC Oost-Nederland’; https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland, file number: 2023–16401). It is registered at ClinicalTrials.gov (NCT06132750; study registration date: 2023-10-05; study first passed date: 2023-11-15).

Digestive system and mitochondrial diseases in children

The article discusses the features of lesions of the digestive system in children with mitochondrial diseases. Mitochondria play an important role in cellular metabolism as they are responsible for producing the majority of cellular energy in the form of adenosine triphosphate. Mutations in mitochondrial genes responsible for the functioning of mitochondria can lead to various forms of mitochondrial diseases. These diseases may present with the following clinical symptoms: muscle weakness, movement disorders, neurological symptoms, impaired motility and absorption from the gastrointestinal tract. Diagnosis of mitochondrial diseases can be challenging due to genetic and clinical heterogeneity. Treatment currently remains a pressing problem, as research in this area is being actively conducted and new methods are emerging aimed at the therapy and treatment of these rare diseases.

Cancer Risk in Patients With Muscular Dystrophy and Myotonic Dystrophy: A Register-Based Cohort Study.

Muscular dystrophies and myotonic disorders are genetic disorders characterized by progressive skeletal muscle degeneration and weakness. Epidemiologic studies have found an increased cancer risk in myotonic dystrophy, although the cancer risk spectrum is poorly characterized. In patients with muscular dystrophy, the cancer risk is uncertain. We aimed to determine the overall cancer risk and cancer risk spectrum in patients with muscular dystrophy and myotonic dystrophy using data from the Swedish National registers. We performed a matched cohort study in all patients with muscular dystrophy or myotonic dystrophy born in Sweden 1950-2017 and 50 matched comparisons by sex, year of birth, and birth county per individual. The association with cancer overall and specific malignancies was estimated using stratified Cox proportional hazard models. We identified 2,355 and 1,968 individuals with muscular dystrophy and myotonic dystrophy, respectively. No increased overall cancer risk was found in muscular dystrophy. However, we observed an increased risk of astrocytomas and other gliomas during childhood (hazard ratio [HR] 8.70, 95% CI 3.57-21.20) and nonthyroid endocrine cancer (HR 2.35, 95% CI 1.03-5.34) and pancreatic cancer (HR 4.33, 95% CI 1.55-12.11) in adulthood. In myotonic dystrophy, we found an increased risk of pediatric brain tumors (HR 3.23, 95% CI 1.16-9.01) and an increased overall cancer risk in adults (HR 2.26, CI 1.92.2.66), specifically brain tumors (HR 10.44, 95% CI 7.30-14.95), thyroid (HR 3.92, 95% CI 1.70-9.03), and nonthyroid endocrine cancer (HR 7.49, 95% CI 4.47-12.56), endometrial (HR 8.32, 95% CI 4.22-16.40), ovarian (HR 4.00, 95% CI 1.60-10.01), and nonmelanoma skin cancer (HR 3.27, 95% CI 1.32-8.13). Here, we analyze the cancer risk spectrum of patients with muscular dystrophy and myotonic dystrophy. To the best of our knowledge, this is the first report of an increased risk for CNS tumors in childhood and adult nonthyroid endocrine and pancreatic cancer in muscular dystrophy. Furthermore, for myotonic dystrophy, we confirmed previously reported associations with cancer and expanded the cancer spectrum, finding an unreported increased risk for nonthyroid endocrine cancer. Additional studies confirming the cancer risk and delineating the cancer spectrum in different genetic subtypes of muscular dystrophies are warranted before considering altered cancer screening recommendations than for the general population.