Types Of Neuromuscular Disorders Research Articles

Chronic Pain in Patients with Spinal Muscular Atrophy in Switzerland: A Query to the Spinal Muscular Atrophy Registry.

Background and Objectives: Chronic pain is a common symptom in various types of neuromuscular disorders. However, for patients with spinal muscular atrophy (SMA), the literature regarding chronic pain is scarce. Thus, this study assessed the prevalence of chronic pain in children, adolescents, and adults with SMA and investigated the influence of clinical characteristics on chronic pain. Materials and Methods: This study used data from 141 patients, which were collected by the Swiss Registry for Neuromuscular Disorders. Extracted data included information on pain (present yes/no, pain location, and pain medication) and clinical characteristics, such as SMA type, motor function, wheelchair use, scoliosis, and contractures. Results: The analyses revealed that the highest prevalence of chronic pain was observed in adolescents with 62%, followed by adults with 48%, children (6-12 years) with 39%, and children < 6 years with 10%. The legs, back, and hips were most frequently reported as pain locations. Sex (females), age (adolescents), and the presence of contractures and scoliosis (with surgery) were factors that were associated with chronic pain. Conclusions: These findings contribute to a better understanding of pain in SMA, shedding light on its prevalence and characteristics in different age groups, which underscores the importance of assessing and managing pain in patients with SMA.

The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement

Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junction diseases, and muscle diseases. Over the years, numerous studies have pointed to protein homeostasis as a crucial factor in the development of these fatal diseases. The ubiquitin–proteasome system (UPS) plays a fundamental role in maintaining protein homeostasis, being involved in protein degradation, among other cellular functions. Through a cascade of enzymatic reactions, proteins are ubiquitinated, tagged, and translocated to the proteasome to be degraded. Within the ubiquitin system, we can find three main groups of enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin–protein ligases). Only the ubiquitinated proteins with specific chain linkages (such as K48) will be degraded by the UPS. In this review, we describe the relevance of this system in NMDs, summarizing the UPS proteins that have been involved in pathological conditions and neuromuscular disorders, such as Spinal Muscular Atrophy (SMA), Charcot–Marie–Tooth disease (CMT), or Duchenne Muscular Dystrophy (DMD), among others. A better knowledge of the processes involved in the maintenance of proteostasis may pave the way for future progress in neuromuscular disorder studies and treatments.

Neuromuscular manifestations of lead poisoning in opium and herbal users in Iran

Opium sale is prohibited in Iran, and sellers mix it with lead to increase the weight. Herein, we describe neuromuscular findings in nine patients who developed lead poisoning due to opium/drug consumption. The mean age of patients was 53±3.5 years and their mean blood lead level was 122.6±20.8μg/dL. Most of the patients had an acute/subacute course presenting as axonal or demyelinating sensorimotor polyneuropathy, motor neuron disease, and multiple mononeuropathies with favorable response to the chelation therapy. Lead poisoning should be considered in patients with a history of opium use and neuromuscular symptoms.

Differential and quantitative neuroimaging characteristics of inclusion body myositis

In clinical settings, it is often difficult to distinguish inclusion body myositis (IBM) from other neuromuscular diseases. In order to clarify clinically useful characteristics for making the differential diagnosis of IBM, we performed clinical, epidemiological, and neuroimaging analyses in patients with various types of neuromuscular disorders. We enrolled 333 patients with myopathy and 12 patients with amyotrophic lateral sclerosis (ALS) who had been hospitalized in our department from January 1, 1979, to December 31, 2018. Among them, 18 patients with IBM, 16 patients with polymyositis (PM), and 12 patients with ALS who showed equivalent severity of muscle weakness in their lower limbs underwent the quantitative neuroimaging analysis using lower limb CT and clinical assessment. Patients with IBM exhibited significantly greater muscular degeneration in the rectus femoris, vastus, sartorius, adductor, anterior calf, and medial gastrocnemius muscles than those with PM or ALS. The ratio of the remaining muscle area of the quadriceps relative to that of the hamstrings and the duration from onset to CT imaging were negatively correlated in patients with IBM, indicating that the anterior thigh muscles were preferentially affected over the posterior muscles. Characteristic muscular degeneration in the lower limbs on CT imaging may aid for making the diagnosis of IBM.

Myopathy pathology

Biopsy of muscle is an essential component of the diagnostic approach for patients with suspected neuromuscular disease. Knowledge of the fundamentals of muscle biopsy pathology is useful for understanding of the pathogenesis of many types of neuromuscular disorders. This talk first provides an introduction to information regarding appropriate biopsy site selection, appropriate biopsy procedures, and correct handling and processing of the tissues. Then, this talk presents normal and pathological appearance of muscle using routine histochemical and immune histological technique and provides the knowledge of basic muscle pathological findings including neurogenic and myopathic features on muscle biopsy. The remainder of this talk provides the key clinical characteristics and pathologic findings on muscle biopsy of certain neuromuscular diseases including muscular dystrophies and inflammatory myopathies.

Different profiles of upper limb function in four types of neuromuscular disorders

The aim of this research was to study impairments, activity limitations and participation restrictions due to upper limb involvement in people with four different types of neuromuscular disorders (NMD) – FacioScapuloHumeral Dystrophy (FSHD), Limb-Girdle Muscular Dystrophy (LGMD), Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD) – and to investigate whether common or different profiles could be identified.Total of 267 respondents with NMD from the Netherlands answered a set of questionnaires covering upper limb impairments (pain and stiffness), activity limitations and participation restrictions. Pain was most often reported by persons with FSHD. Problems in the FSHD group were mainly characterized by relatively high scores for pain and stiffness and low scores for activity limitations. People with LGMD reported also low scores for activity limitations. Conversely, people with SMA and DMD experienced in general relatively low scores for pain and stiffness and high scores for activity limitations. Although people with FSHD and LGMD had relatively few activity limitations, all NMD groups experienced restrictions when participating in social activities.Our results indicate specific profiles of upper limb function in different types of NMD. While the profile observed in persons with FSHD seems to reflect overuse, the profile seen in persons with DMD and SMA is suspicious of disuse, each requiring a specific rehabilitation strategy.

Should hydrogen therapy be included in a musculoskeletal medicine routine?

Molecular hydrogen (H 2) has recently been recognized as a potential novel therapeutic agent in biomedicine. Initially proposed to be a possible treatment for certain types of neuromuscular disorders, cardio-metabolic diseases and cancer, H 2 improved clinical end-points and surrogate markers in several clinical trials, mainly acting as an anti-inflammatory agent and powerful antioxidant. In this paper, the medicinal properties of H 2 in musculoskeletal medicine are discussed with the aim to provide an updated and practical overview for health professionals working in this field.

Should hydrogen therapy be included in a musculoskeletal medicine routine?

Molecular hydrogen (H 2) has recently been recognized as a potential novel therapeutic agent in biomedicine. Initially proposed to be a possible treatment for certain types of neuromuscular disorders, cardio-metabolic diseases and cancer, H 2 improved clinical end-points and surrogate markers in several clinical trials, mainly acting as an anti-inflammatory agent and powerful antioxidant. In this paper, the medicinal properties of H 2 in musculoskeletal medicine are discussed with the aim to provide an updated and practical overview for health professionals working in this field.

Prevalence of neuromuscular disorders in Qena governorate/Egypt: population-based survey

Background: Few epidemiological studies of the prevalence of neuromuscular disorders have been undertaken. The aim of the study was to estimate the prevalence of the most common types of neuromuscular disorders in Qena governorate/Egypt.Methods: A random sample was taken from 11 districts, involving 9303 inhabitants with 57.3% urban residents and 42.7% rural residence. Patients were diagnosed using a screening questionnaire for the diagnosis of neuromuscular disorders. All positive cases were referred to Qena University hospital where they underwent full clinical, electrophysiological, and laboratory investigations.Results: Out of 9303 participants 448 cases were identified positive during survey. Four hundred and twenty-six cases proved to have neuromuscular disorders giving a crude prevalence rate (CPR) of 4.57%; 408 cases had definite neuropathy and 18 cases had muscular disorders equivalent to CPR of 4.39% and 193/105 respectively. There was a higher prevalence in the rural than urban population. The CPR of focal compression neuropathies was 1.8%, with the majority of cases having carpal tunnel syndrome (CPR = 1.67%). CPR of diabetic neuropathy was 1.67%. The CPR of compressive radiculopathy was 0.34%. Traumatic nerve injury had a CPR 0.06%. The lifetime prevalence of Bell’s palsy was 0.16%. Hereditary motor and sensory neuropathy had a CPR 0.08%. The CPR of idiopathic neuropathy was 0.09% and Infective Leprotic neuropathy was 0.04%. Five patients were diagnosed as having muscular dystrophy and another 5 patients had myotonia with CPR of 54/105 for each. Two cases of myasthenia gravis and another two cases with systemic myopathy were recorded giving a CPR of 21/105.Conclusion: The overall CPR of neuromuscular disorders in the general population in Qena governorate/Egypt was higher than reported in other countries.

Understanding the experience of myotonic dystrophy. Mixed method study.

Myotonic Dystrophy (DM) is a progressive multi-systemic disorder characterized by myotonia and muscle weakness where currently no effective treatment or cure to prevent or delay the disorder exists. This study used mixed methods to examine the experience of living with DM, in patients and their close relatives. Thirteen patients and eight next of kin responded completing Quality of Life and Psychological distress questionnaires in this cross-sectional study, and participating in a semi-structured interview. The findings indicate a higher level of anxiety and hopelessness in next of kin compared to patients, while patients were more depressed. Next of kin reported higher physical, but lower emotional quality of life than patients. Qualitative interviews confirmed the questionnaire findings. The findings from this study may be helpful in genetic counseling. Genetic counselors and geneticists should not only be aware of the burden of being a next of kin, but include discussions about opportunities to minimize the burden in families affected with DM. The findings may be of relevance in counseling for other types of neuromuscular disorders.

Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges

Inherited peripheral neuropathies (IPN) are one of the most frequent inherited causes of neurological disability characterized by considerable phenotypic and genetic heterogeneity. Based on clinical and electrophysiological properties, they can be subdivided into three main groups: HMSN, dHMN, and HSN. At present, more than 50 IPN genes have been identified. Still, many patients and families with IPN have not yet received a molecular genetic diagnosis because clinical genetic testing usually only covers a subset of IPN genes. Moreover, a considerable proportion of IPN genes has to be identified. Here we present results of WES in 27 IPN patients excluded for mutations in many known IPN genes. Eight of the patients received a definite diagnosis. While six of these patients carried bona fide pathogenic mutations in known IPN genes, two patients had mutations in genes known to be involved in other types of neuromuscular disorders. A further group of eight patients carried sequence variations in IPN genes that could not unequivocally be classified as pathogenic. In addition, combining data of WES and linkage analysis identified SH3BP4, ITPR3, and KLHL13 as novel IPN candidate genes. Moreover, there was evidence that particular mutations in PEX12, a gene known to cause Zellweger syndrome, could also lead to an IPN phenotype. We show that WES is a useful tool for diagnosing IPN and we suggest an expanded phenotypic spectrum of some genes involved in other neuromuscular and neurodegenerative disorders. Nevertheless, interpretation of variants in known and potential novel disease genes has remained challenging.

Neuromuscular disorders and Takotsubo syndrome

Takotsubo syndrome (TTS, apical ballooning, stress cardiomyopathy, transient left ventricular dysfunction, broken heart syndrome) is characterised by a reversible mid-segmental left ventricular dysfunction of which the pathogenesis remains speculative but which is said to be due to enhanced central or focal sympathetic stimulation, triggered by emotional or physical stress [ 1 Porto I. Della Bona R. Leo A. et al. Stress cardiomyopathy (tako-tsubo) triggered by nervous system diseases: a systematic review of the reported cases. Int J Cardiol. 2013; 167: 2441-2448 Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar , 2 Tsuchihashi K. Ueshima K. Uchida T. et al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris–Myocardial Infarction Investigations in Japan. J Am Coll Cardiol. 2001; 38: 11-18 Abstract Full Text Full Text PDF PubMed Scopus (1336) Google Scholar ]. TTS has been occasionally reported in association with neuromuscular disorders (NMDs) but it is unclear how frequently TTS is associated with NMDs and which types of NMDs are associated with TTS. Aim of this literature search was to investigate how frequently TTS is associated with a NMD, which MIDs have been described in association with TTS, and if NMDs contribute to the pathogenesis of TTS.

Sugammadex reversal of rocuronium-induced neuromuscular blockade in two types of neuromuscular disorders: Myotonic dystrophy and spinal muscular atrophy

Neuromuscular disorders like myotonic dystrophy (dystrophia myotonica or Steinert's disease) and spinal muscular atrophy are associated with perioperative complications related to muscle weakness. These patients have an increased sensitivity to non-depolarising neuromuscular blocking agents, which can lead to postoperative residual curarization (PORC) and its associated respiratory complications. Adequate reversal of neuromuscular blockade is essential to prevent this. Sugammadex is the first selective relaxant binding agent and it reverses rocuronium- and vecuronium-induced neuromuscular block. Two cases are reported in which the patients received sugammadex to reverse a rocuronium-induced neuromuscular block. Reversal of the rocuronium-induced neuromuscular block (NMB) in both cases was fast, effective and without recurarization, and no safety concerns were observed.

Practicing with Weighted Vests Induces Neuromechanical Changes in Countermovement Jump

Jumping with preloaded vest is proposed as a method of warm up that leads to an increase in the height of subsequent jumps. However, the biomechanical adaptations during loaded jumps are still unknown. PURPOSE: The aim of this study was to explore the adaptive changes in the biomechanics of the lower limb joints during loaded maximal jumping. METHODS: Following a full set of warm-up jumps, healthy college students (10 male, 8 female, 64.4±16.3 kg, 1.7±0.809 m) were asked to perform 2 pre-test jumps with a loaded vest equal to 15% of their body mass. Following which, they performed 3 sets of 5 consecutive countermovement jumps (exercise set). This was followed by a post-test where the subject again jumped twice. The jumps of pre and post exercise set were compared. Kinetic and kinematic data were collected for 12 defined body segments. Subjects would be excluded from the study if they had any history of ankle sprain or any type of neuromuscular disorder. RESULTS: A significant increase in weighted jump height in males was observed during the post-test (28.45 vs. 26.48 cm, p-value <.01), an effect not seen in the females (18.9 vs. 18.5 cm, p-value <.01). This is consistent with the findings of Komi et al. (1977), who observed that during both drop jumps and counter movement jumps, males have better performances than women. Males also demonstrated significant increases in peak hip and knee angle, while females showed no significant changes in joint kinematics and kinetics. We also observed a significant increase in hip joint power and a decrease in ankle joint power. CONCLUSION: Increased range of motion in the knee and hip as well as a shift in joint power from distal to proximal joints may be the underlying strategy that resulted in increased post-test jump height. Perhaps, the lack of change in joint power and range of motion in females prevented them from increasing the jump height. One possible mechanistic explanation is a difference in joint and tendon stiffness between genders, which Komi et al. (1978) have suggested previously. From a practical perspective, these findings suggested that gender should play a role in the use of loaded jumping as a training procedure.

Non-invasive positive ventilation in the treatment of sleep-related breathing disorders

This chapter addresses the use of long-term non-invasive positive pressure ventilation (NIPPV) (to the exclusion of continuous positive airway pressure) in the different clinical settings in which it is currently proposed: principally in diseases responsible for hypoventilation characterized by elevated PaCO 2. Nasal masks are predominantly used, followed by nasal pillow and facial masks. Mouthpieces are essentially indicated in case daytime ventilation is needed. Many clinicians currently prefer pressure-preset ventilator in assist mode as the first choice for the majority of the patients with the view of offering better synchronization. Nevertheless, assist-control mode with volume-preset ventilator is also efficient. The settings of the ventilator must insure adequate ventilation assessed by continuous nocturnal records of at least oxygen saturation of haemoglobin-measured by pulse oximetry. The main categories of relevant diseases include different types of neuromuscular disorders, chest-wall deformities and even lung diseases. Depending on the underlying diseases and on individual cases, two schematic situations may be individualized. Either intermittent positive pressure ventilation (IPPV) is continuously mandatory to avoid death in the case of complete or quasi-complete paralysis or is used every day for several hours, typically during sleep, producing enough improvement to allow free time during the daylight in spontaneous breathing while hypoventilation and related symptoms are improved. In case of complete or quasi-complete need of mechanical assistance, a tracheostomy may become an alternative to non-invasive access. In neuromuscular diseases, in kyphosis and in sequela of tuberculosis patients, NIPPV always significantly increases survival. Conversely, no data support a positive effect on survival in chronic obstructive pulmonary disease.

The reliability and validity of a self-report version of the FIM instrument in persons with neuromuscular disease and chronic pain

Jensen MP, Abresch RT, Carter GT. The reliability and validity of a self-report version of the FIM instrument in persons with neuromuscular disease and chronic pain. Objective To evaluate the reliability and validity of a self-report version of the FIM instrument (FIM-SR). Design Survey study. Setting Rehabilitation research program. Participants Adults with neuromuscular disorders (NMD) and chronic pain (N=141). Interventions Not applicable. Main outcome measures The FIM-SR and Medical Outcomes 36-Item Short-Form Health Survey (SF-36). Results The internal consistency coefficients of the FIM-SR scales were all adequate to excellent (Cronbach α range, .73–.98; median, .96). Correlations between the FIM-SR scales and SF-36 scales supported the concurrent validity of the former. Also, the FIM-SR scales associated with motor function discriminated between those subjects who reported being ambulatory and those who reported requiring use of a wheelchair or other assistive device for getting around. Finally, FIM-SR scales discriminated between different types of NMDs, with patients with amyotrophic lateral sclerosis showing significantly lower scores on the FIM-SR self-care, motor, and total scores than all other NMD diagnostic groups, and showing significantly lower scores on the FIM-SR sphincter control, mobility, and locomotion scales than most of the other diagnostic groups. Conclusions The FIM-SR scales appear to be reliable and valid measures of independence in 6 specific (self-care, sphincter control, mobility, locomotion, communication, social cognition), and 3 global (motor, cognition, total) areas of functioning in persons with NMD.

Muscle ultrasound in children: Normal values and application to neuromuscular disorders

In this study, 105 healthy children (45 to 156 months old, 57 girls) were examined using ultrasound (US) imaging to obtain reference values of muscle dimensional and aspect parameters. We measured biceps and quadriceps sizes and subcutaneous tissue thickness. To quantify muscle aspect, we calculated muscle density, inhomogeneity and white-area index by digital image analysis. Age-, weight- and gender-dependencies were discussed. We demonstrated earlier that the complete set of parameters allows for differentiation between myopathies and neuropathies in adults, with high sensitivity. In this study, we investigated if these parameters have additional value in the diagnostic evaluation of 36 children with proven neuromuscular disease (20 Duchenne muscular dystrophy, 16 neuropathies). We found that density analysis provides a sensitive method for distinguishing between healthy children and children with neuromuscular disorders. We have also found that more detailed aspect analysis is necessary to further distinguish between these types of neuromuscular disorders in children. In conclusion, this set of normal muscle parameters can be used to help diagnose neuromuscular disorders in children. It will also facilitate follow-up in disease progression and therapy. (E-mail: n.m.maurits@neuro.azg.nl)