Neuromuscular Junction Disorders

The three main components of the neuromuscular junction (NMJ) include the presynaptic region, the synaptic cleft, and the postsynaptic region. The NMJ acts as an interface between the motor nerve and muscle by converting the motor nerve electric currents into chemical signals and then back into electric currents in the muscle. This chapter reviews electrodiagnostic testing in NMJ disorders, including repetitive nerve stimulation and single-fiber electromyography. Myasthenia gravis, congenital myasthenic syndromes, Lambert-Eaton myasthenic syndrome, botulism, and organophosphate poisoning and other toxins are discussed, including epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Tables include an overview of neuromuscular disorders, drugs with adverse effects on the NMJ, common immunomodulatory agents used for treatment of myasthenia gravis, congenital myasthenic syndromes, and toxins and venoms. Figures illustrate the NMJ structure and function, structure of the presynaptic and postsynaptic regions, electrodiagnostic studies in NMJ disorders, and dysfunction of the NMJ in acetylcholine receptor myasthenia gravis. This chapter contains 5 highly rendered figures, 5 tables, 65 references, and 5 MCQs.

Neuromuscular Junction Disorders

10.2310/im.6267 ◽

2015 ◽

Author(s):

Anthony A Amato ◽

Mohammad Kian Salajegheh

Keyword(s):

Neuromuscular Junction ◽

Myasthenia Gravis ◽

Motor Nerve ◽

Neuromuscular Disorders ◽

Synaptic Cleft ◽

Organophosphate Poisoning ◽

Electric Currents ◽

The three main components of the neuromuscular junction (NMJ) include the presynaptic region, the synaptic cleft, and the postsynaptic region. The NMJ acts as an interface between the motor nerve and muscle by converting the motor nerve electric currents into chemical signals and then back into electric currents in the muscle. This chapter reviews electrodiagnostic testing in NMJ disorders, including repetitive nerve stimulation and single-fiber electromyography. Myasthenia gravis, congenital myasthenic syndromes, Lambert-Eaton myasthenic syndrome, botulism, and organophosphate poisoning and other toxins are discussed, including epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Tables include an overview of neuromuscular disorders, drugs with adverse effects on the NMJ, common immunomodulatory agents used for treatment of myasthenia gravis, congenital myasthenic syndromes, and toxins and venoms. Figures illustrate the NMJ structure and function, structure of the presynaptic and postsynaptic regions, electrodiagnostic studies in NMJ disorders, and dysfunction of the NMJ in acetylcholine receptor myasthenia gravis. This review contains 5 highly rendered figures, 5 tables, and 65 references.

Congenital myasthenic syndromes in adult neurology clinic

Neurology ◽

10.1212/wnl.0000000000006478 ◽

2018 ◽

Vol 91 (19) ◽

pp. e1770-e1777 ◽

Cited By ~ 9

Author(s):

Justin C. Kao ◽

Margherita Milone ◽

Duygu Selcen ◽

Xin-Ming Shen ◽

Andrew G. Engel ◽

...

Keyword(s):

Myasthenia Gravis ◽

Clinical Laboratory ◽

Age At Onset ◽

Diagnostic Delay ◽

Muscle Diseases ◽

Seronegative Myasthenia Gravis ◽

Neurology Clinic ◽

ObjectiveTo investigate the diagnostic challenges of congenital myasthenic syndromes (CMS) in adult neuromuscular practice.MethodsWe searched the Mayo Clinic database for patients with CMS diagnosed in adulthood in the neuromuscular clinic between 2000 and 2016. Clinical, laboratory, and electrodiagnostic data were reviewed.ResultsWe identified 34 patients with CMS, 30 of whom had a molecular diagnosis (14 DOK7, 6 RAPSN, 2 LRP4, 2 COLQ, 2 slow-channel syndrome, 1 primary acetylcholine receptor deficiency, 1 AGRN, 1 GFPT1, and 1 SCN4A). Ophthalmoparesis was often mild and present in 13 patients. Predominant limb-girdle weakness occurred in 19 patients. Two patients had only ptosis. Age at onset ranged from birth to 39 years (median 5 years). The median time from onset to diagnosis was 26 years (range 4–56 years). Thirteen patients had affected family members. Fatigable weakness was present when examined. Creatine kinase was elevated in 4 of 23 patients (range 1.2–4.2 times the upper limit of normal). Repetitive nerve stimulation revealed a decrement in 30 patients. Thirty-two patients were previously misdiagnosed with seronegative myasthenia gravis (n = 16), muscle diseases (n = 15), weakness of undetermined cause (n = 8), and others (n = 4). Fifteen patients received immunotherapy or thymectomy without benefits. Fourteen of the 25 patients receiving pyridostigmine did not improve or worsen.ConclusionMisdiagnosis occurred in 94% of the adult patients with CMS and causes a median diagnostic delay of nearly 3 decades from symptom onset. Seronegative myasthenia gravis and muscle diseases were the 2 most common misdiagnoses, which led to treatment delay and unnecessary exposure to immunotherapy, thymectomy, or muscle biopsy.

Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain

Genes ◽

10.3390/genes11050539 ◽

2020 ◽

Vol 11 (5) ◽

pp. 539

Author(s):

Lidia Gonzalez-Quereda ◽

Maria Jose Rodriguez ◽

Jordi Diaz-Manera ◽

Jorge Alonso-Perez ◽

Eduard Gallardo ◽

...

Keyword(s):

Next Generation Sequencing ◽

Neuromuscular Disorders ◽

Neuromuscular Disorder ◽

Gene Panel ◽

Muscular Dystrophies ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing ◽

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.

Classification of myasthenia gravis and congenital myasthenic syndromes in dogs and cats

Journal of Veterinary Internal Medicine ◽

10.1111/jvim.15855 ◽

2020 ◽

Vol 34 (5) ◽

pp. 1707-1717

Author(s):

Thomas Mignan ◽

Mike Targett ◽

Mark Lowrie

Keyword(s):

Myasthenia Gravis ◽

Morphologic and immunopathologic findings in myasthenia gravis and in congenital myasthenic syndromes.

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.43.7.577 ◽

1980 ◽

Vol 43 (7) ◽

pp. 577-589 ◽

Cited By ~ 57

Author(s):

A G Engel

Keyword(s):

Myasthenia Gravis ◽

Genetic Landscape of Congenital Myasthenic Syndromes From Turkey: Novel Mutations and Clinical Insights

Journal of Child Neurology ◽

10.1177/0883073817705252 ◽

2017 ◽

Vol 32 (8) ◽

pp. 759-765 ◽

Cited By ~ 10

Author(s):

Uluç Yiş ◽

Kerstin Becker ◽

Semra Hız Kurul ◽

Gökhan Uyanik ◽

Erhan Bayram ◽

...

Keyword(s):

Cholinesterase Inhibitors ◽

Neuromuscular Disorders ◽

Genetic Diagnosis ◽

Common Type ◽

Child Neurology ◽

Novel Mutations ◽

Genetic Landscape ◽

Prompt Diagnosis ◽

Congenital myasthenic syndromes are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, the authors report on cases with genetically proven congenital myasthenic syndromes from Turkey. The authors retrospectively reviewed their experience of all patients with congenital myasthenic syndromes, referred over a 5-year period (2011-2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven congenital myasthenic syndromes originating from Turkey. In total, the authors identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n = 15; 35%) were the most common type, followed by synaptic basal-lamina associated (n = 14; 33%) and presynaptic syndromes (n = 10; 23%). The authors had only 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n = 1; 2%). Knowledge on congenital myasthenic syndromes and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.

Electrodiagnostic Findings in Neuromuscular Disorders

10.1093/med/9780190603434.003.0004 ◽

2018 ◽

Author(s):

Bashar Katirji

Keyword(s):

Neuromuscular Junction ◽

Peripheral Nerve ◽

Myasthenia Gravis ◽

Nerve Conduction ◽

Neuromuscular Disorders ◽

Nerve Conduction Studies ◽

Anterior Horn Cell ◽

Peripheral Neuropathies ◽

Peripheral Nerve Lesions ◽

Myasthenic Syndrome

Neuromuscular disorders are often classified into four major categories: anterior horn cell disorders, peripheral neuropathies, neuromuscular junction disorders and myopathies. This chapter discusses the electrodiagnostic and clinical EMG findings in these various neuromuscular disorders. Peripheral neuropathies are subdivided into focal mononeuropathies, radiculopathies, plexopathies and generalized peripheral polyneuropathies. Focal peripheral nerve lesions and generalized peripheral polyneuropathies may be axonal or demyelinating, and manifest quite distinctly on nerve conduction studies. Neuromuscular junction disorders may be presynaptic, as seen with the Lambert-Eaton myasthenic syndrome, or postsynaptic, as seen with myasthenia gravis.

Myasthenia gravis and congenital myasthenic syndromes in dogs and cats: A history and mini-review

Neuromuscular Disorders ◽

10.1016/j.nmd.2016.03.002 ◽

2016 ◽

Vol 26 (6) ◽

pp. 331-334 ◽

Cited By ~ 11

Author(s):

G. Diane Shelton

Keyword(s):

Myasthenia Gravis ◽

Electrodiagnostic Examination of the Tibial Nerve in Clinically Normal Ferrets

Veterinary Medicine International ◽

10.4061/2010/756321 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Ezio Bianchi ◽

Daniela Callegari ◽

Manuela Ravera ◽

Maurizio Dondi

Keyword(s):

Action Potentials ◽

Motor Nerve ◽

Neuromuscular Disorders ◽

Low Frequency ◽

Mustela Putorius ◽

Motor Nerve Conduction ◽

Clinically Normal ◽

Minimum Latency ◽

Muscular Action

Tibial nerves of 10 normal domestic ferrets (Mustela putorius furo) were evaluated by means of electrodiagnostic tests: motor nerve conduction studies (MNCSs), supramaximal repetitive nerve stimulation (SRNS),Fwaves, and cord dorsum potentials (CDPs). Values of conduction velocity, proximal and distal compound muscular action potentials, and amplitudes of MNCS were, respectively, 63.25 7.56 m/sec, 10.79 2.75 mV, and 13.02 3.41 mV. Mean decrements in amplitude and area of compound muscular action potentials of wave 9 with low frequency SRNS were 0.3 3.83% and 0.1 3.51%. The minimum latency of theFwaves and theFratio were, respectively, 8.49 0.65 ms and 1.92 0.17. Onset latency of CDP was 1.99 0.03 ms. These tests may help in diagnosing neuromuscular disorders and in better characterizing the hindlimb paresis reported in many ferrets with systemic illnesses.