Effects of Specialized Care Orthoses on Walking and Personal Goals in Adults with Leg Muscle Weakness Due to Neuromuscular Disorders

Introduction 238 Assessment 239 Treatment 240 A variety of neuromuscular disorders may affect the ventilatory pump at different sites (Table 37.1). Most of these disorders result in respiratory muscle weakness, which results in alveolar hypoventilation and impaired cough. Patients with known neuromuscular disease may present acutely with a presentation related to their underlying neuromuscular disease (such as infection) or occasionally in end-stage ventilatory failure....

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Impairment of Synaptic Vesicle Exocytosis and Recycling During Neuromuscular Weakness Produced in Mice by 2,4-Dithiobiuret

Journal of Neurophysiology ◽

10.1152/jn.00934.2001 ◽

2002 ◽

Vol 88 (6) ◽

pp. 3243-3258 ◽

Cited By ~ 4

Author(s):

You-Fen Xu ◽

Dawn Autio ◽

Mary B. Rheuben ◽

William D. Atchison

Keyword(s):

Synaptic Vesicle ◽

Muscle Weakness ◽

Nerve Stimulation ◽

Synaptic Vesicles ◽

Motor Nerve ◽

Neuromuscular Disorders ◽

Neuroaxonal Dystrophy ◽

Nerve Terminals ◽

Synaptic Vesicle Exocytosis ◽

Vesicle Exocytosis

Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy. DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear. The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing. We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness. Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K+depolarization. Terminals ranged from those with nearly normal fluorescence (“bright terminals”) to terminals that were poorly labeled (“dim terminals”). Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable. A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals. Two findings suggest that posttetanic “slow endocytosis” remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles. In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block withd-tubocurarine. Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by α-latrotoxin. Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness. The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing.

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Flow-volume loop changes reflecting respiratory muscle weakness in chronic neuromuscular disorders

The American Journal of Medicine ◽

10.1016/0002-9343(87)90897-7 ◽

1987 ◽

Vol 83 (4) ◽

pp. 673-680 ◽

Cited By ~ 44

Author(s):

Walter G. Vicken ◽

Murray G. Elleker ◽

Manuel G. Cosio

Keyword(s):

Muscle Weakness ◽

Respiratory Muscle ◽

Neuromuscular Disorders ◽

Flow Volume ◽

Respiratory Muscle Weakness ◽

Flow Volume Loop

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Molecular basis of impaired muscle function in a mouse model of congenital myopathy due to compound heterozygous RYR1 mutations

The Journal of General Physiology ◽

10.1085/jgp.2021ecc26 ◽

2021 ◽

Vol 154 (9) ◽

Author(s):

Alexis Ruizl ◽

Jan Eckhardt ◽

Susan Treves ◽

Francesco Zorzato

Keyword(s):

Mouse Model ◽

Malignant Hyperthermia ◽

Muscle Weakness ◽

Muscle Function ◽

Fiber Type ◽

Neuromuscular Disorders ◽

Extraocular Muscles ◽

Malignant Hyperthermia Susceptibility ◽

Compound Heterozygous ◽

Feeding Difficulties

Congenital myopathies (CM) are a group of early-onset, genetically diverse muscle disorders of variable severity with characteristic muscle biopsy findings. Mutations in RYR1, the gene encoding the RYR1, are the most common genetic cause, responsible for ∼30% of all human CM. They are linked to the pharmacogenetic disorder malignant hyperthermia susceptibility and to various disease phenotypes, including central core disease (which is primarily dominantly inherited), multiminicore disease (which is predominantly recessively inherited), some forms of centronuclear myopathy and congenital fiber-type disproportion (which can be either dominantly or recessively inherited), and King–Denborough syndrome (a CM characterized by skeletal abnormalities, dysmorphic features, and malignant hyperthermia susceptibility). The recessive forms of RYR1-linked CM are more severe, affecting children at birth and, in addition to profound muscle weakness, may also affect facial and extraocular muscles and cause skeletal deformities and feeding difficulties. To study the mechanism leading to the profound muscle weakness characterized by recessive RYR1-CM, we created transgenic mice knocked in for the compound heterozygous RYR1 p.Q1970fsX16+p.A4329D mutations (double knock-in mouse, or DKI) identified in a severely affected child. The in vivo and ex vivo physiological functions of fast twitch, slow twitch, and extraocular muscles were severely impaired in DKI mice; in addition, the mutations were accompanied by a >50% decrease in RYR1 protein in all muscles examined, as well as changes in the expression of many proteins important for muscle function and chromatin structure. Muscle ultrastructure was disorganized, with fewer CRU and mitochondria and presence of cores. MyHC-EO, the superfast and ocular-muscle−specific myosin heavy isoform, was almost undetectable in EOMs from DKI mutant mice. Thus, the DKI mouse model faithfully recapitulates the human disease and could be exploited for preclinical studies aimed at developing therapeutic strategies to treat neuromuscular disorders linked to recessive RYR1 mutations.

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Periodik Paralisis Hipokalemia pada Anak Usia 15

Jurnal Kedokteran Syiah Kuala ◽

10.24815/jks.v20i2.18506 ◽

2020 ◽

Vol 20 (2) ◽

Author(s):

Jufitriani Ismy

Keyword(s):

Key Words ◽

Clinical Symptom ◽

Muscle Weakness ◽

Lower Leg ◽

Periodic Paralysis ◽

Progressive Muscle Weakness ◽

Leg Muscle ◽

Acute Attacks ◽

Muscle Groups

Abstrak. Periodik paralisis hipokalemia menyebabkan kelemahan otot yang progresif terutama pada kelompok otot proksimal tungkai bawah, serangan akut dapat terjadi secara berulang. Serangan pertama biasanya terjadi antara usia 5 tahun dan 35 tahun, tetapi frekuensi serangan paling tinggi antara usia 15 dan 35 tahun. Ditemukan kasus Periodik paralisis hipokalemia yang berulang pada anak laki laki usia 15 tahun. Semua hasil analisis gejala klinis dan pemeriksaan penunjang sangat mendukung untuk diagnosis periodik paralisis hipokalemia.Kata kunci: periodik paralisis hipokalemia, kelemahan otot, usia 15 tahunAbstract. Periodic paralysis of hypokalemia causes progressive muscle weakness especially in the proximal lower leg muscle groups, acute attacks may occur repeatedly. The first attacks usually occur between the ages of 5 and 35, but the frequency of attacks is highest between the ages of 15 and 35. A case of recurrent hypokalemia periodic paralysis was found in a boy aged 15 years. All the results of clinical symptom analysis and investigations are very supportive for the diagnosis of periodic hypokalemia paralysis. Key words: periodic hypokalemia paralysis, muscle weakness, age 15 years

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A Man with Progressive Leg Muscle Weakness 20 Years After an Acute Paralysis This case was reported in Narayanaswami P and Bertorini T: Progressive amyotrophy as a late complication of myelopathy. J Neurol Sci 184:11–13, 2001.

Neuromuscular Case Studies ◽

10.1016/b978-0-7506-7332-7.50041-6 ◽

2008 ◽

pp. 245-248

Author(s):

Tulio E. Bertorini

Keyword(s):

Muscle Weakness ◽

Late Complication ◽

Leg Muscle

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Muscle Weakness

10.1093/med/9780190226459.003.0073 ◽

2017 ◽

Author(s):

L. Jane Easdown

Keyword(s):

Patient Outcomes ◽

Muscle Weakness ◽

Neuromuscular Disorders ◽

Perioperative Period ◽

Neuromuscular Blocking ◽

Common Finding ◽

Neuromuscular Blocking Drugs ◽

Assessment And Treatment ◽

Common Etiology ◽

Prompt Diagnosis

Muscle weakness in the perioperative period is a common finding and is a risk to patient safety. It can occur as a result of many physiological, pathological, and iatrogenic states. The most common etiology is the use of, misuse of, and failure to reverse neuromuscular blocking drugs (NMBDs). Patients might also present with underlying neuromuscular disorders at baseline or in an exacerbated state after surgery and anesthesia. Muscle weakness can lead to critical events such as respiratory failure and can delay recovery and discharge. The plan for prompt diagnosis and management of a patient with muscle weakness is presented. Knowledge of the pathophysiology, assessment, and treatment of perioperative muscle weakness is essential to ensure optimal patient outcomes.

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Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

European Journal of Translational Myology ◽

10.4081/ejtm.2016.5962 ◽

2016 ◽

Vol 26 (4) ◽

Cited By ~ 1

Author(s):

Andreas Totzeck ◽

Petra Mummel ◽

Oliver Kastrup ◽

Tim Hagenacker

Keyword(s):

Myasthenia Gravis ◽

Calcium Channel ◽

Muscle Weakness ◽

Neuromuscular Disorders ◽

Intravenous Immunoglobulins ◽

Voltage Gated ◽

Dropped Head Syndrome ◽

Seronegative Myasthenia Gravis ◽

Myasthenic Syndrome ◽

Voltage Gated Calcium Channel

Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

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Isolated proximal weakness of the legs due to neuroborreliosis

BMJ Case Reports ◽

10.1136/bcr-2021-244431 ◽

2021 ◽

Vol 14 (11) ◽

pp. e244431

Author(s):

Simone Nibourg ◽

Martijn Beudel ◽

Jeroen Trip

Keyword(s):

Differential Diagnosis ◽

Muscle Weakness ◽

Neuromuscular Disorders ◽

Proximal Muscle Weakness ◽

Proximal Muscle ◽

Diagnostic Challenge ◽

Intravenous Antibiotics ◽

Treatable Condition

Proximal muscle weakness of the legs is a symptom with a broad differential diagnosis. It is mainly caused by neuromuscular disorders and is often a diagnostic challenge. Here, we present a 73-year-old man with isolated proximal weakness of the legs due to lumbar root involvement on the basis of neuroborreliosis. After treatment with intravenous antibiotics he recovered completely. This is the first described case with isolated proximal muscle weakness of the legs due to neuroborreliosis. Despite the fact neuroborreliosis is a rare cause of proximal muscle weakness of the legs, clinicians should include it in their differential diagnosis, especially since it is a treatable condition.

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