Percutaneous Electrical Nerve Stimulation (PENS) for Infrapatellar Saphenous Neuralgia Management in a Patient with Myasthenia gravis (MG).

Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness of the cranial and skeletal muscles, however, neuropathies are extremely rare. In this case report we present a case of a 61-year-old man diagnosed Myasthenia gravis who came to our attention due to a 1 week of acute deep pain [NPRS 8/10] in the anterior and medial right knee which occurred during walking [NPRS 8/10] or stair climbing [NPRS 9/10]. A complete medical record and clinical examination based on physical exploration and ultrasound assessment confirmed a infrapatellar saphenous neuralgia. Therapeutic interventions included Percutaneous nerve electrical stimulation combined with pain neuroscience education, neural mobilization of the saphenous nerve and quadriceps resistance exercises. After 4 weeks, pain intensity [NRPS = 1/10], knee functionality [OKS = 41/48] and lower limb functionality [LLFI = 80%] were notably improved, nevertheless, fatigue [RPE = 2/10] was similar than baseline. At 2 months of follow-up, the effect on intensity of pain NRPS [0/10] and functionality OKS [40/48] and LLFI [82%] was maintained, however, no significant clinical changes were detected on perceived fatigue RPE Scale [2/10]. Despite the important methodological limitations of this study, our case report highlights the efficacy of percutaneous electrical nerve stimulation combined with physical agents modalities for pain and functionality of infrapatellar saphenous neuralgia in the context of Myasthenia gravis.

Effectiveness of modified Buzhong Yiqi decoction in treating myasthenia gravis: study protocol for a series of N-of-1 trials.

BACKGROUND: Myasthenia gravis (MG) is an acquired autoimmune disease with high heterogeneity. The disease is chronic, relapsing repeatedly and progressive with acute exacerbation occasionally. Although the treatment of MG has developed, it is still unsatisfactory and has some unexpected side effects. Traditional Chinese medicine (TCM) has shown great potential in MG treatment, including relief of muscle weakness syndrome, improvement of patient's quality of life, and reduction of side effects of western medicine. The purpose of this study is to evaluate the effectiveness of modified Buzhong Yiqi decoction (MBYD) as an add-on therapy for MG through a small series of N-of-1 trials. METHODS: Single-centre, randomized, double-blind, 3 crossover N-of-1 trials will be conducted to enroll patients with MG diagnosed as spleen-stomach deficiency syndrome or spleen-kidney deficiency syndrome in TCM. Each N-of-1 trial has 3 cycles of two 4-week periods containing the MBYD period and placebo period. The wash-out interval of 1 week is prior to switching each period. PRIMARY OUTCOME: quantitative myasthenia gravis (QMG). SECONDARY OUTCOMES: the following scales: myasthenia gravis composite (MGC), myasthenia gravis activities of daily living profile (MG-ADL), myasthenia gravis quality of life (MG-QOL); the level of CD4+FoxP3+Treg cells and cytokines (IL-4, IL-17A, INF-γ, TGF-ß) in the peripheral blood; the alterations of the composition of gut microbiota; reduction of the side effects of western medicine. DISCUSSION: Used by WinBUGS software, we will conduct a hierarchical Bayesian statistical method to analyze the efficacy of MBYD in treating MG in individuals and populations. Some confounding variables such as TCM syndrome type and potential carryover effect of TCM will be introduced into the hierarchical Bayesian statistical method to improve the sensitivity and applicability of the trials, and the use of prior available information within the analysis may improve the sensitivity of the results of a series of N-of-1 trials, from both the individual and population level to study the efficacy of TCM syndrome differentiation. We assumed that this study would reveal that MBYD is effective for MG and provide robust evidence of the efficacy of TCM to treat MG. TRIAL REGISTRATION: Chinese Clinical Trial Register, ID: ChiCTR2000040477 , registration on 29 November 2020.

[Exploration on the diagnosis and treatment of generalized myasthenia gravis with acupuncture and moxibustion based on the study of ancient medical works].

Through collecting the relevant provisions and medical cases of wei syndrome treated with acupuncture and moxibustion from ancient medical works, the diagnosis and acupoint selection in treatment of generalized myasthenia gravis (gMC) with acupuncture and moxibustion were analyzed systematically from 3 aspects, i.e. meridian differentiation, disease differentiation and syndrome differentiation. In treatment based on meridian differentiation, the acupoints are selected in the light of the running course of meridian and characteristics of meridian disorders. In treatment based on disease differentiation, the acupoints are selected in accordance with etiology, pathogenesis and transmission stages of wei syndrome. Concerning to syndrome differentiation in treatment, the acupoints are selected on the basis of therapeutic principles determined by different syndromes/patterns of wei syndrome. In modern clinical practice, the treatment for gMC should be rooted at ancient literature, thus a standardized regimen can be developed for diagnosis and treatment with acupuncture and moxibustion.

Direct comparison of median and ulnar repetitive nerve stimulation in generalized myasthenia gravis.

INTRODUCTION/AIMS: Ulnar nerve repetitive nerve stimulation (RNS) has been traditionally used in the electrophysiological evaluation of myasthenia gravis (MG). However, its low diagnostic sensitivity remains a limitation. Existing data may suggest that median nerve RNS outperforms that of the ulnar nerve, but a direct comparison is currently lacking. The aim of this study was to directly compare the diagnostic yields between median and ulnar nerve RNS in patients with generalized MG. METHODS: We performed a retrospective analysis of patients with MG who underwent median and ulnar nerve RNS at a single tertiary center. RESULTS: RNS studies of median nerve recording from the abductor pollicis brevis and ulnar nerve recording from the adductor digiti minimi were completed in 28 patients with generalized MG. Abnormal RNS was more frequently observed in the median compared with the ulnar nerve (60.7% vs 35.7%, P = .046). The average magnitude of decrement was higher in the median nerve compared with the ulnar nerve (17.3% vs 9.6%, P = .017). Differences between the median and ulnar nerve RNS studies were restricted to patients with mild manifestations (Myasthenia Gravis Foundation of America class II). DISCUSSION: Median nerve RNS has superior diagnostic sensitivity as compared with ulnar nerve RNS in the assessment of mild generalized MG.

A case of YY1-associated syndromic learning disability or Gabriele-de Vries syndrome with myasthenia gravis.

Exome sequencing is being used increasingly to evaluate patients with intellectual disability. YY1 is a ubiquitously distributed transcription factor belonging to the GLIKruppel class of zinc finger proteins recently recognized as the causative gene in 23 patients for the Gabriele-de Vries syndrome. We report a new case with similar features and a novel variant in YY1, in a region of the gene, which has not previously been reported. A 25 year old female was referred to clinical genetics with a diagnosis of autoimmune myasthenia gravis, facial dysmorphism and learning disability. Chromosomal microarray and gene panel test for congenital myasthenic syndrome was negative. Whole exome sequencing (WES) revealed a presumed pathogenic de novo novel, heterozygous, truncating variant in the YY1 gene, c.860_864delTTAAAA, p.Ile287Argfs*3. The Ile287 residue is conserved across species and is situated in the transcription repressor domain of the protein. This variant is novel and lies in a domain of the protein where no previously reported variants occur. The phenotypic features of our case closely match those of the reported patients. Autoimmune myasthenia gravis has not been reported in these patients and may constitute an expansion of this phenotypic spectrum or perhaps more likely a second unrelated diagnosis.

Anti-MuSK Antibody-positive Myasthenia Gravis Successfully Treated with Outpatient Periodic Weekly Blood Purification Therapy.

A 37-year-old man with anti-muscle-specific tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) presented with subacute progressive dysphagia and muscle weakness of the neck and bilateral upper extremities. Conventional immune-suppressive treatments and high-dose intravenous immunoglobulin were ineffective. He then displayed repeated exacerbations and remissions over the course of two years, despite two to four sessions of plasma exchange (PE) every two months. The patient was successfully treated with outpatient periodic weekly blood purification therapy with alternative PE and double-filtration plasmapheresis using an internal shunt. This case report suggests the benefits of blood purification therapy with an internal shunt against anti-MuSK antibody-positive MG.

Accuracy of the ice test in the diagnosis of myasthenic ptosis.

BACKGROUND: Diagnosis of myasthenia gravis is difficult, especially when the disease is restricted to ocular muscles. It is a well-known observation that myasthenic ptosis improves with cold and based on this, the ice pack test has been used as a tool in its differential diagnosis. The aim of the study is to investigate the diagnostic value of ice pack test as a preliminary test in the differential diagnosis of myasthenia and to find out the percentage of positivity and negativity of the ice pack test. MATERIALS AND METHODS: The study included patients seeking treatment for ptosis in a tertiary care center in Kerala. All patients were subjected to the ice pack test. Evaluation of patients was made by recording the marginal reflex distance (MRD). MRD was recorded before and after the application of ice pack, and an improvement of more than 2 mm was considered positive. Patients were divided into two groups: (1) those who had ptosis and features suggestive of myasthenia; and, (2) those who had ptosis but no features of myasthenia. Patients of both groups were subjected to relevant investigations and the diagnosis of myasthenia was established. RESULTS: Ice cold test was positive in 48 (96%) patients and negative in two patients of the myasthenia group. In the control group, 6 (12%) patients had a false positive ice cold test and in the remaining 44 patients (88%), ice cold test was negative. CONCLUSION: Ice pack test has a high specificity and sensitivity in the differential diagnosis of myasthenic ptosis.

Repetitive facial nerve stimulation in myasthenia gravis 1min after muscle activation is inferior to testing a second muscle at rest.

OBJECTIVES: To explore the increased diagnostic yield of repetitive nerve stimulation (RNS) following activation for myasthenia gravis (MG) diagnosis, and compare with testing an additional muscle at rest only. METHODS: We performed a retrospective chart review of patients diagnosed with MG attending the neuromuscular clinic from 2013 to 2015 and extracted data on electrophysiological studies, including frequency of decrement of 10% or above, with facial RNS at rest, and following activation. RESULTS: The total cohort included 102 patients with MG, 65 with generalized, and 37 with ocular MG. Facial RNS sensitivities for diagnosing MG were 32-46% and 14-19% respectively. The increase in RNS sensitivity following muscle activation was 6-8% for frontalis muscle recordings, and 0-2% for nasalis muscle recordings. Recording from both muscles at rest only, increased the sensitivity by 9-15%. CONCLUSION: RNS is a valid method for confirming a clinical diagnosis of MG. The increased diagnostic yield of RNS following activation is controversial. Our study shows that the increased diagnostic yield of facial RNS following activation is modest, and is less than performing facial RNS in a second muscle. SIGNIFICANCE: Performing facial RNS in an additional muscle at rest appears to be more sensitive than facial RNS in a single muscle after activation.

Ocular myasthenia gravis accompanied by anosmia.

We report a case of ocular myasthenia gravis (MG) accompanied by anosmia. A 76-year-old man had idiopathic anosmia of 2-year duration. Four months before consultation, he began to have drooping in the right upper eyelid along with muscle soreness, distension, and pain in the nape. His tongue was dark-red with a thin and white coating; his pulse was wiry and slippery. According to Traditional Chinese Medicine, eyelid drooping and anosmia are the main signs of liver constraint and spleen deficiency. In Western Medicine, the diagnosis was ocular MG and idiopathic anosmia. Our patient, along with the literature, suggests that anosmia may be an early symptom before MG. MG accompanied by anosmia could be a special subtype of MG according to antibody production and symptoms.

The clinical absolute and relative scoring system-a quantitative scale measuring myasthenia gravis severity and outcome used in the traditional Chinese medicine.

Myasthenia gravis (MG) is a chronic autoimmune disease caused by autoantigen against the nicotine acetylcholine receptor at the neuromuscular junction. With modern treatment facilities, the treatment effect and outcome for MG has been greatly improved with MG and non-MG patients enjoying the same life expectancy. Many classifications of disease distribution and severity have been set up and tested all over the world, mainly in the western world. However, the absolute and relative scoring system for evaluating the severity and treatment effect of MG in China where traditional Chinese medicine (TCM) has been practiced for thousands of years has not been introduced worldwide. The TCM has achieved a great success in the treatment of MG in the country with a huge population. This article serves to introduce this scoring system to the world.

Electrophysiological profile of the patients with MuSK positive myasthenia gravis.

OBJECTIVES: To determine the electrophysiological profile of our cohort of patients with muscle-specific tyrosine kinase (MuSK) positive myasthenia gravis (MG). METHODS: Repetitive nerve stimulation test (RNS) and jitter analysis using concentric needle electrode were performed in 31 MuSK and in 28 acetylcholine receptor (AChR) positive MG patients. RESULTS: Pathological RNS was verified in 16 (51.6%) MuSK and 26 (92.9%) AChR MG patients (P < 0.01). Pathological jitter analysis was registered in 28 (90.3%) MuSK and 26 (92.9%) AChR MG patients (P > 0.05). Increased jitter was present in extensor digitorum communis (EDC) in 23 (74.2%) MuSK and in 25 (89.3%) AChR MG patients (P > 0.05) as well as in orbicularis oculi (OO) muscle in 24 (85.7%) MuSK and 22 (81.5%) AChR MG patients (P > 0.05). Lower mean value of mean consecutive difference (MCD) and fewer potential pairs with increased jitter were registered in MuSK MG compared to AChR MG patients only in EDC muscle (P < 0.05). In MuSK MG patients, increased jitter was observed to be more frequent in patients with longer disease duration (P < 0.05) and also in those patients exhibiting more severe disease forms (P < 0.01) only in EDC muscle. DISCUSSION: Repetitive nerve stimulation test has low sensitivity in MuSK MG patients, while jitter analysis shows high sensitivity, especially in facial muscles. The EDC muscle in MuSK MG patients usually shows increased jitter in more severe disease forms and later in the course of the disease.

[Autoantibody against the presynaptic P/Q-type voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome].

Antibodies against the muscle acetylcholine receptor (AChR) were recognized as the cause of myasthenia gravis in the 1970s'. Since then, other neurological disorders associated with autoantibodies have been identified, each associated with an antibody against a ligand- or voltage-gated ion channel. Autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs) are detected in patients with Lambert-Eaton myasthenic syndrome (LEMS). These antibodies interfere with the calcium-dependent release of acetylcholine from the presynaptic membrane. LEMS is an autoimmune disorder affecting the neuromuscular junction, and is characterized by proximal muscle weakness, reduction of tendon reflex, and autonomic dysfunction. Electrophysiological examinations show small-amplitude compound muscle action potentials and increments on rapid repetitive nerve stimulation. Fifty to sixty percent of LEMS patients present with tumors, mostly small cell lung carcinoma (SCLC), as a paraneoplastic syndrome. SCLC is a neuroendocrine tumor, which expresses neuronal VGCCs. Some patients present cerebellar ataxia, which is always accompanied by SCLC. These patients tend to show higher titers of VGCC antibodies than that by LEMS patients with no ataxia. The diagnosis can be confirmed by finding reduced compound muscle action potential amplitudes at rest that shows increments greater than 100% with repetitive nerve stimulation and antibody detection by using radioimmunoprecipitation assays. The treatment options are generally categorized as anti-tumor, immunomodulating, immunosuppressing, and symptomatic treatments. In cases with SCLC, effective treatment against the tumor can improve LEMS. Plasmapheresis and intravenous administration of high-dose immunoglobulins have a short effect. Prednisone, alone or in combination with immunosuppressants can achieve long-term control of the disorder.

A cohort study on myasthenia gravis patients in China.

Clinical classification and age distribution in myasthenia gravis (MG) cases seem different between Oriental and Caucasian populations, but there have rarely been any clinical studies on MG patients from mainland China. The goal of the current study was to perform a comprehensive survey of myasthenia gravis in a hospital in China, establishing contemporary cohort data and clinical features. 1,108 unselected patients with MG attending the 309th Hospital of PLA, Beijing, China were studied during a 36-month period from July 2008 to June 2011. The sex ratio was 1:1 (F:M). 62.5 % of patients presented as adolescents and adults. Ocular MG cases accounted for 65.6 % childhood MG patients. A positive response was observed in 96.8 % of the patients for neostigmine tests, whereas a positive decremental response to low frequency repetitive nerve stimulation (RNS) was observed in 77.4 % of the patients. The highest stimulating positive rate was 65.3 % in stimulated facial nerve. Thymoma was significantly increased in those patients with severe MG, especially in the cohort involving the respiratory muscles (p < 0.001). The study revealed higher frequency of ocular and childhood MG compared to other studies in USA and European countries, which can be a result of optimum case ascertainment, increased disease duration, or application of complex diagnostic tests. The relative increase in the prevalence of ocular myasthenia can be attributed to the impact of an aging population.

[Analysis of the clinical manifestations and electrophysiological changes in 32 patients with atypical myasthenia gravis].

OBJECTIVE: To study the clinical characteristics and electrophysiological changes in patients with atypical myasthenia gravis (MG). METHODS: The characteristics of the clinical symptoms and electrophysiological changes were investigated in 32 patients with atypical MG diagnosed in our hospital from January 2004 to December 2008. RESULTS: The ages of the patients ranged from 7 to 70 years. Five patients were diagnosed to have ocular MG (OMG), among whom 2 patient only complained of eye discomfort and blurred vision. Twenty-seven patients had generalized MG, and 6 of them showed muscle weakness of the limbs with or without mild difficulty in swallowing or respiratory muscles, but free of muscle dysfunctions in muscles of eyes, head, neck or face. Another 2 patients manifested muscular atrophy. Twenty-three patients (71.9%) displayed both fluctuating symptoms and positive results of fatigue test. Twenty-nine patients (90.6%) have positive results in the neostigmine test. Two patients in the OMG group (40.0%) showed positive results in the low frequency repetitive nerve stimulation (LFRNS), as compared with the 21 patients in the generalized MG group (71.9%) showing positive results. The total positivity rate of LFRNS was 71.9% in the total patients, consistent with the published data. CONCLUSIONS: In MG patients with atypical clinical symptoms, negative results of neostigmine test and fatigue test, LFRNS test can be an indispensable method to increase detection rate of MG and reduce erroneous or missed diagnosis.

The difficulty in confirming clinical diagnosis of myasthenia gravis in a seronegative patient: a possible neurophysiological approach.

In seronegative myasthenia gravis repetitive nerve stimulation and single-fibre EMG have a crucial diagnostic value but they may be negative, particularly in repetitive nerve stimulation studies. We report the case of a 43-year-old patient with generalized seronegative myasthenia gravis with negative 3 Hz repetitive nerve stimulation at Erb's point and voluntary single-fibre EMG in the orbicularis oculi. We also performed 6 and 12 Hz repetitive nerve stimulation at Erb and stimulated single-fibre EMG in the extensor digitorum communis and our findings were pathological. Our data suggest that, for individual patients with an atypical picture characterised by dissociation between a severe clinical pattern and no definite neurophysiological findings on conventional tests, repetitive nerve stimulation with a stimulation rate higher than 3 Hz and/or stimulated single-fibre EMG with an increasing stimulation rate may be helpful.

Comparison of amplitude and area decrement in repetitive nerve stimulation.

OBJECTIVE: To access the percentage of the patients whose repetitive nerve stimulation (RNS) studies were negative for 10% amplitude decrement but positive for 10% area decrement and to compare these disagreed results with specialist physician's diagnosis. STUDY DESIGN: Retrospective descriptive study. SETTING: Electrodiagnosis laboratory, Department of Rehabilitation Medicine, King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: All of the electromyography (EMG) reports of RNS studies were reviewed Both 10% amplitude and area decrement were used as criteria for diagnosis in each patient. The disagreed results would be compared to final diagnosis of the specialist physicians that were recorded in out-patient medical records. RESULTS: Eighty-three reports were included in the present study. Nineteen records (22.9%) were negative for 10% amplitude decrement but positive for 10% area decrement. Three records (3.6%) were positive for 10% amplitude decrement but negative for 10% area decrement. Twenty-two patients had disagreed results. Sixteen disagreed out-patient medical records (72.7%) were available for review the final specialist doctors' diagnosis. About 69% of patients, whose test was negative for 10% amplitude decrement but positive for 10% area decrement, were diagnosed as myasthenia gravis (MG) or suspected MG. All of the patients, whose test was negative for 10% area decrement but positive for 10% amplitude decrement, were diagnosed as MG. The use of both 10% amplitude and area decrement instead of 10% amplitude decrement alone will provide additional diagnostic yields in about 13% of the cases. CONCLUSION: Twenty-three percent of patients had disagreed RNS results that were negative for 10% amplitude decrement but positive for 10% area decrement. When these disagreed results were compared to the final diagnosis of specialist doctors, 69% of these patients were diagnosed or suspected and treated as MG. Using both 10% amplitude and area decrement may improve sensitivity of MG diagnosis in about 13% of the cases.

[Establishment and analysis of serum two-dimensional gel electrophoresis profiles of myasthenia gravis patients with spleen and kidney deficiency syndrome].

OBJECTIVE: The purpose of this study was to establish two-dimensional gel electrophoresis (2-DE) profiles of serum of myasthenia gravis patients, and to identify the differential proteomic expressions between normal persons and myasthenia gravis patients with spleen and kidney deficiency syndrome. METHODS: Samples of serum protein were extracted by repeated freeze-thaw method and separated by two-dimensional electrophoresis. Differential proteomic expressions between the myasthenia gravis patients and the normal control persons were identified by two-dimensional polyacrylamide gel electrophoresis, silver staining, image-master 2-DE software analysis, peptide mass fingerprinting based on matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), BioWorks and NCBI software database searching. RESULTS: The two-dimensional polyacrylamide gel electrophoresis profiles of serum proteins were successfully established by 2-DE. Twenty-one of the significant differential proteins were selected and identified by MALDI-TOF-MS. Eight of them were finally identified. CONCLUSIONS: The 2-DE profiles of serum proteins were established and the differential proteomic expressions were identified by proteome technique in our study. This can be an experimental basis for further research of the pathogenesis and treatment of myasthenia gravis.

Juvenile limb-girdle myasthenia gravis.

Limb-girdle myasthenia is a rare disorder which includes familial and autoimmune forms. Myasthenia gravis is an uncommon disease in children and its diagnosis may be difficult. We report here five cases of autoimmune juvenile LGM starting before the age of 16 years with attention to clinical diagnostic difficulties, evolution, laboratory and instrumental data as well as response to treatment. Diagnosis of limb-girdle myasthenia requires a strong index of suspicion also in childhood. We suggest that this form be suspected in children with unclassifiable myopathy, mostly affecting deltoid muscles and lower extremities.

Miastenia gravis en el anciano: experiencia de un hospital comarcal en una patología emergente / Myasthenia gravis in the elderly: a county hospital experience of an emerging disease

Objetivo: evidenciar el significativo incremento de la incidencia de miastenia gravis (MG) en la población anciana, así como conocer las particularidades del manejo de esta enfermedad en esos pacientes. Metodología: análisis retrospectivo de los casos de MG en pacientes mayores de 65 años atendidos en el hospital comarcal de la Merced de Osuna, Sevilla, durante los años 1995 a 2003.Resultados: obtuvimos una serie de 9 pacientes (5 varones y 4 mujeres) con una edad media de 77,6 (ñ 8,6) años y edad media de inicio de 68,1 (ñ 13,8) años. El tiempo medio de evolución era de 9,3 (ñ 11) años. Ocho pacientes (88,8 por ciento) presentaron MG de inicio tardío. Clínicamente 7 pacientes (77,7 por ciento) presentaron la forma ocular (grupo I) y 2 la generalizada (22,3 por ciento), uno leve (grupo IIa) y otro moderada (grupo IIb). Los síntomas oculares fueron las manifestaciones clínicas iniciales preponderantes (88,8 por ciento). Sólo uno de los pacientes presentó timoma. Los anticuerpos antirreceptores de acetilcolina (Ac-AchR) fueron positivos en todos los casos. Todos los pacientes recibieron tratamiento con piridostigmina, y en 5 pacientes (55,5 por ciento) se usaron además esteroides. No se produjo ninguna muerte, aunque en 3 enfermos (33,3 por ciento) los resultados del tratamiento fueron peores. Conclusiones: es necesario cambiar el concepto clásico de MG como patología del adulto joven y considerarla, como refleja nuestro estudio, como una patología emergente en la población anciana. Creemos que la MG es una enfermedad que debemos conocer, dado que la detección y el tratamiento precoces consiguen generalmente una mejoría física y funcional del paciente mayor (AU)