Incidence Of Myasthenia Gravis Research Articles

The Incidence of Myasthenia Gravis in the Province of Ferrara, Italy, in the Period of 2008-2022: An Update on a 40-Year Observation and the Influence of the COVID-19 Pandemic.

Myasthenia gravis (MG) is the most common neuromuscular junction disorder. We evaluated the MG incidence rate in the province of Ferrara, Northern Italy, over two time frames (2008-2018 and 2019-2022, i.e., the COVID-19 pandemic) and considered early-onset (EOMG), late-onset (LOMG), and thymoma- and non-thymoma-associated MG. Moreover, in the second period, we assessed its possible relationship with SARS-CoV-2 infection or COVID-19 vaccination. We used a complete enumeration approach to estimate the MG incidence and its temporal trend. For the period of 2008-18, 106 new cases were identified (mean incidence rate 2.7/100,000 people). The highest rates were observed for the over-70 age group and in rural areas, with 17% of thymoma-associated MG. During the COVID-19 period, 29 new cases were identified (average incidence rate 2.1/100,000 people), showing a marked (though not statistically significant) decrease in the mean annual incidence compared to the previous period. Again, the highest rate was observed for the over-70 age group. The first period was in line with our previous observations for the period between 1985 and 2007, highlighting a rising incidence of LOMG and a marked decrease in EOMG. During the COVID-19 period, incidence rates were lower in the first years whereas, when the pandemic ended, the previous trend was confirmed.

Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.

In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.

Characteristics of myasthenia gravis in elderly patients: a retrospective study.

The incidence of myasthenia gravis (MG) is increasing, and its characteristics in elderly patients are believed to differ from those in younger patients. However, only a few studies have focused on elderly patients with MG. To review the characteristics of MG in elderly patients and evaluate whether older age is an independent factor associated with achieving minimal manifestation status (MMS). This retrospective cohort study included 367 patients (319 non-elderly and 48 elderly patients) with MG enrolled at Xiangya Hospital from September 1, 2016, to December 31, 2018. We collected demographic data and information regarding comorbidities, antibody status, Myasthenia Gravis Foundation of America classification, affected muscle groups, thymoma, and treatment. MMS was defined as the primary outcome. Comorbidities were more common in elderly than in younger patients with MG. Anti-acetylcholine receptor antibody was the dominant subtype, whereas anti-muscle-specific tyrosine kinase antibody was rare and detected only in non-elderly patients. Elderly patients were more likely than younger patients to have generalized MG, but the frequency of thymoma was lower (28.5% vs. 10.4%, p = 0.0078). MMS or better was achieved in 154 (48.3%) and 13 (27.1%) non-elderly and elderly patients, respectively. Older age did not appear to be an independent factor associated with MMS (hazard ratio = 0.625; 95% confidence interval, 0.345-1.131). Older age was not an independent factor for a worse prognosis in patients with MG. The treatment of elderly patients with MG should be individually tailored.

The incidence of myasthenia gravis in the republic of Moldova before and during the COVID-19 pandemic

The incidence of myasthenia gravis in the republic of Moldova before and during the COVID-19 pandemic

Analysis of clinical manifestations and diagnosis of late-onset myasthenia gravis

Introduction. Myasthenia gravis is one of the most common autoimmune neuromuscular diseases, the peak incidence is in the age of 20–40 years. However, studies show that throughout the world in recent decades there has been an increase in the prevalence and incidence of myasthenia gravis among older people.Purpose of the study – to evaluate the clinical manifestations and diagnostic features of myasthenia gravis in patients with an onset of diseases in the elderly.Materials and methods. The retrospective, non-interventional study included 315 patients over 18 years old with a reliable (3 out of 4 criteria) and an undoubted (4 out of 4 criteria) diagnosis of myasthenia gravis, the duration of the disease for up to 5 years, undergoing inpatient treatment from 2001 to 2017 years. The severity of the clinical manifestations of myasthenia gravis was assessed using the Myasthenia Gravis Foundation of America scale. We were taken into account the information about the first symptoms, duration of the period from the onset of the disease to the verification of the diagnosis, results of the examinations, the presence of concomitant diseases and treatment methods.Results. The most common symptom of myasthenia gravis in the group of patients with debut disease aged 60 years and older was ptosis (p <0.001). The crises and pathology of the thymus were less common in elderly patients (p <0.0001). The concentration of antibodies to acetylcholine receptors was the same (p = 0.05) among all patients. The level of antibodies to titin was increased in patients with lateonset (p = 0.0014). The presence of bronchopulmonary pathology made worse the course of myasthenia gravis in elderly people (p = 0.01), while cardiovascular and cerebrovascular diseases, as well as diabetes mellitus, did not occur (p >0.005). At the first examination in the group of elderly patients among the incorrectly diagnoses prevailed: stroke or decompensation of chronic cerebral ischemia (p = 0.0002). With a comparable duration and severity of myasthenia gravis in different age groups, the combination of anticholinesterase drugs, glucocorticosteroids and azathioprine (p = 0.01) at a lower daily dose (100 mg) was more often used for the treatment of elderly patients compared with young and middle-aged groups (150 mg) (p = 0.03).Conclusion. Diagnosis of myasthenia gravis in elderly patients presents the greatest difficulties, and symptoms of manifestation during initial treatment are often regarded as a manifestation of vascular pathology. Despite the presence of concomitant diseases characteristic of this age group, myasthenia gravis does not differ in the severity of the course. To achieve remission and compensation of symptoms, elderly patients do not need large doses of symptomatic and pathogenetic drugs.

Epidemiologic studies of myasthenia gravis: literature review

The review of domestic and foreign literature devoted to epidemiological studies of myasthenia gravis has been reviewed. The article presents data on the prevalence and incidence of myasthenia gravis in several regions of Russia and abroad. The prevalence of myasthenia gravis in the world varies, according to different authors, in a very wide range – from 2.17 to 32.0 per 100 thousand people. There are few epidemiological studies of myasthenia gravis in large cities and regions of Russia. Meanwhile, studies of the prevalence and incidence of myasthenia gravis are a necessary stage in the work to increase the effectiveness of diagnosis and treatment of this pathology, to determine the need for specialized types of medical care. The results of these studies can be used to optimize the management of myasthenia gravis patients.

Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia

The incidence of myasthenia gravis which is characterized by progressive muscular weakness on the background of structural disorders of the thymus, has increased. Myasthenia gravis is a multifactorial autoimmune disease, it has a pronounced clinical heterogeneity, and therefore the standard diagnostic and treatment protocol is not always effective. To substantiate an individual approach to the treatment of various clinical forms of myasthenia, we conducted a study of mechanisms and markers of loss of central and peripheral self-tolerance in thymus-independent myasthenia (M) and thymus-dependent myasthenia gravis with thymus hyperplasia (MH) and thymoma (MT), involving a total of 427 patients examined. In patients with different phenotypes of myasthenia, we used the methods of spectrophotometry, flow cytometry, enzyme immunoassay. In patients with MH on the background of lymphofollicular thymus hyperplasia we revealed a pronounced humoral sensitization in comparison with the reference values: the concentration of C4 complement, C-reactive protein, circulating immune complexes and the initiation of an indirect autoimmune reaction a reliable increase in autoantibodies (AAbs) to the α1 and α7 subunit of subunit of nicotinic receptors (nAChR). In M and MT groups a high similar titer of AAbs to other epitopes was revealed: DNA, β2-glycoprotein I, membranes of intestinal and stomach cells, lung, liver, kidney cells. A pronounced blast-transforming response to the presence of the mitogen PHA was revealed in the MT group. In the MT group, a decrease in the content of CD4+ CD28+ co-stimulatory molecules and in the MH group, a decrease in СD4+ CD25+ Treg lymphocytes was revealed. Individual methods for correcting the loss of self-tolerance in patients with different clinical phenotypes of myasthenia were justified taking into account the use of immunosuppression, specific viral-neutralizing immunoglobulins and massive IgG immunoglobulin therapy, and the application of anti-inflammatory recombinant interleukins.

Application of Postoperative Chemotherapy on Thymomas and Its Prognostic Effect

背景与目的探讨术后化疗在胸腺肿瘤中的应用及术后化疗对Masaoka Ⅲ期/Ⅳ期预后的影响。方法1994年3月至2012年12月, 中国胸腺瘤研究协作组(Chinese Alliance of Research for Thymomas, ChART)数据库共纳入2, 306例胸腺肿瘤病例, 资料相对完整1, 700例患者纳入本研究, 对其中Masaoka Ⅲ期/Ⅳ期665例患者进行进一步分析, 初步评估术后化疗的临床价值, 采用Kaplan-Meier法绘制不同亚组患者生存曲线, Cox回归进行多因素分析影响预后的因素。采用倾向值匹配研究(propensity-matched study, PSM), 评估化疗的临床价值。结果1, 700例患者中未行术后化疗1, 406例(82.7%), 术后化疗294例(17.3%), 随着Masaoka分期的增加, 术后化疗患者的比例也随之增高, 差异有统计学意义(P<0.001)。对Masaoka Ⅲ期/Ⅳ期患者665例进行进一步分析, 其中未术后化疗组444例, 术后化疗组221例。两组患者在有无重症肌无力、WHO病理类型、病理分期、手术根治性、有无术后放疗等方面分布有差异(P<0.05)。其中C型胸腺瘤、不完全切除和术后放疗明显影响患者术后复发和生存(P<0.05)。术后化疗组5年和10年无病生存率分别为51%、30%, 5年和10年复发率分别为46%、68%, 而未术后化疗组5年和10年无病生存率分别为73%、58%。5年和10年复发率分别为26%、40%, 两组无病生存率和复发率均有明显统计学差异(P=0.001, P=0.001)。对有无重症肌无力, 病理类型, 病理分期, 手术根治性状态, 术后放疗等因素进行倾向值匹配筛选出其中158例未术后化疗和158例术后化疗共316例患者, 生存分析显示:未术后化疗组和术后化疗组两组5年生存率并无明显统计学差异(P=0.332)。结论病理学类型、手术的根治性和术后放疗是影响进展期胸腺肿瘤患者术后生存和复发的主要因素。术后化疗并未给Masaoka-Koga Ⅲ期/Ⅳ期胸腺瘤患者带来生存获益。

The application of postoperative chemotherapy in thymic tumors and its prognostic effect.

To study the role of postoperative chemotherapy and its prognostic effect in Masaoka-Koga stage III and IV thymic tumors. Between 1994 and 2012, 1,700 patients with thymic tumors who underwent surgery without neoadjuvant therapy were enrolled for the study. Among them, 665 patients in Masaoka-Koga stage III and IV were further analyzed to evaluate the clinical value of postoperative chemotherapy. The Kaplan-Meier method was used to obtain the survival curve of the patients divided into different subgroups, and the Cox regression analysis was used to make multivariate analysis on the factors affecting prognosis. A Propensity-Matched Study was used to evaluate the clinical value of chemotherapy. Two-hundred and twenty-one patients were treated with postoperative chemotherapy, while the rest 444 cases were not. The two groups showed significant differences (P<0.05) regarding the incidence of myasthenia gravis, World Health Organization (WHO) histological subtypes, pathological staging, resection status and the use of postoperative radiotherapy. WHO type C tumors, incomplete resection, and postoperative radiotherapy were significantly related to increased recurrence and worse survival (P<0.05). Five-year and 10-year disease free survivals (DFS) and recurrence rates in patients who underwent surgery followed by postoperative chemotherapy were 51% and 30%, 46% and 68%, comparing with 73% and 58%, 26% and 40% in patients who had no adjuvant chemotherapy after surgery (P=0.001, P=0.001, respectively). In propensity-matched study, 158 pairs of patients with or without postoperative chemotherapy (316 patients in total) were selected and compared accordingly. Similar 5-year survival rates were detected between the two groups (P=0.332). Pathologically higher grade histology, incomplete resection, and postoperative radiotherapy were found to be associated with worse outcomes in advanced stage thymic tumors. At present, there is no evidence to show that postoperative chemotherapy may help improve prognosis in patients with Masaoka-Koga stage III and IV thymic tumors.

Myasthenia gravis incidence in a general North Atlantic isolated population.

There are no previous studies undertaken about myasthenia gravis in the Faroe Islands. The aim of this study was to establish the incidence of onset of this disease in the Faroese population. Patients were ascertained and registered prospectively from 1986 to 2013 when they were examined at the Neurological Clinic of the Faroese National Hospital or at a private neurological practice, which constitutes all the available neurological services in the Faroe Islands. Twelve new diagnoses were made over a 27-year period, providing an incidence density rate of 9.4 per million person-years (95% confidence limit 4.9-16.5). At presentation, nine of 12 patients had generalized myasthenia gravis and two patients had pure ocular disease, and in one patient, the symptoms were restricted to the bulbo-facial muscles. The sex ratio was 2:1, F/M. In nine of the cases, a positive result of acetylcholine receptor antibody assay was documented. In all patients, there was a beneficial response to anticholinesterase administration. The result yielded no strong evidence of a difference in incidence between that found in the Faroe Islands and those in most European studies, apart from recent studies from London, UK; Norway; Spain, and Italy in which incidences from 21 to 30 per million person-years had been reported.

Myasthenia gravis epidemiology in a national cohort; combining multiple disease registries

There is a wide variation in reported prevalence and incidence of myasthenia gravis (MG). In this study, we aimed to evaluate the validity of two nationwide databases by comparing prevalence and incidence rates reported from three recent studies using the two databases as case-finding method. Two different Norwegian nationwide databases were used: the acetylcholine receptor antibody database (reference cohort) and the Norwegian Prescription Database (NorPD) (study cohort). Presence of acetylcholine receptor antibodies (AChR) is specific for MG. Up to 85% of MG patients are AChR antibody-positive. All samples from the whole country were tested at one laboratory. NorPD contains patient information on all prescriptions of pyridostigmine. Prevalence was 131 per million in the study cohort and 145 per million estimated from the reference cohort (Jan 1, 2008). No significant difference in prevalence between the study cohort and the reference cohort was found (SIR 1.1, 95% CI 1.0-1.2). The annual incidence rate was 16.0 per million in the study cohort and 8.8 per million estimated from the reference cohort, twofold more new MG patients were found in the study cohort compared to estimated figures from the reference cohort (SIR 1.8; 1.4-2.3). This study confirms an optimal and unbiased case finding in both databases. Our calculated prevalence and incidence rates are in line with previous population-based studies. There was good agreement in prevalence reported from the two databases. The discrepancy in incidence is expected to diminish as years of study are increasing in NorPD.

Preoperative CT Findings of Thymoma are Correlated with Postoperative Masaoka Clinical Stage

Both preoperative computed tomography (CT) staging and postoperative surgical Masaoka clinical staging are of great clinical importance for diagnosing thymomas. Our study aimed to investigate the relationships between these two staging systems. This was a retrospective review of 129 patients who had undergone thymoma surgery. Helical CT and 16-slice CT were performed preoperatively. Surgical findings were evaluated according to the Masaoka clinical staging system. A significant association was shown between Masaoka clinical staging and CT staging, especially of features including tumor size(P = .004), tumor shape (P < .001), tumor density (P < .001), capsule completeness (P < .001), and involvement of surrounding tissues (P < .001). Based on the CT findings, there were 35.09% of Masaoka stage I patients who had a tumor size <5 cm as compared to 14.81% of stage IV patients. Only 8.77% of Masaoka stage I patients had a tumor size ≥10 cm as compared to 40.74% of stage IV patients. Instages III and IV, most tumors were irregularly shaped with an uneven density and incomplete capsule. Invasive tumors were more frequently found in stages III (81.48%) and IV (88.89%) than in stages I (0%) and II (38.89%). The incidence of myasthenia gravis was comparable in different stages. Consistency between CT and Masaoka clinical stages was higher in stage I (37.98%) than other stages (approximately 10%). This study documented a close relationship between preoperative CT thymoma staging and postoperative Masaoka clinical staging. Thus, preoperative CT findings can be beneficial for determining the proper management and prognosis of thymoma patients.

Minimally Invasive Thymectomy and Open Thymectomy: Outcome Analysis of 263 Patients

An open thymectomy is a morbid procedure. If a minimally invasive thymectomy is performed without compromising the tenets of thymic surgery, it has the potential for decreasing morbidity and may offer similar clinical and oncologic results. This is an institutional review board-approved, retrospective study of a single center's experience with both open (transsternal) and minimally invasive (video-assisted thoracoscopic surgery) thymectomy. Survival estimates and statistical comparisons were calculated using standard software. From 2000 to 2011, 263 patients (93 men; median age, 49 years; interquartile range, 37 to 60 years) underwent thymectomy for indications including myasthenia gravis (n=139) and mediastinal mass (n=108). Seventy-seven thymectomies were performed by minimally invasive approach. Both groups were equally stratified by sex, body mass index, World Health Organization and Masaoka-Koga staging, incidence of myasthenia gravis, and comorbidities except hyperlipidemia and diabetes. The minimally invasive thymectomy cohort had significantly shorter hospital (p<0.01) and intensive care unit lengths of stay (p<0.01) and a lower estimated blood loss (p<0.01). There was an insignificant difference in postoperative cardiac and respiratory complication rates as well as vocal cord paralysis (p=0.60). There was no difference in terms of operative room times (p=0.88) or volume of blood products transfused (p=0.16) between the two groups. Higher estimated blood loss was associated with higher intensive care unit admission rates (p<0.01). All minimally invasive thymoma resections were complete, with negative margins. Minimally invasive thymectomy is safe and achieves a comparable resection and postoperative complication profile when used selectively for all indications, including myasthenia gravis and small thymomas without vascular invasion.

Robot-assisted thymectomy is superior to transsternal thymectomy

Complete thymectomy is the procedure of choice in the treatment of thymomas and in treating selected patients with myasthenia gravis. Transsternal thymectomy is the gold standard for most patients. Robot-assisted thymectomy has emerged as an alternative to open transsternal surgery. The goal of this study was to compare perioperative outcomes in patients who underwent transsternal or robot-assisted thymectomy. We performed a retrospective review of all patients who underwent robot-assisted or transsternal thymectomy at our institution from February 2001 to February 2010. Data are presented as mean±SD. Significance was set as P<0.05. Fifty patients underwent either transsternal (n=35) or robot-assisted (n=15) thymectomy. Patient demographics and the incidence of myasthenia gravis were similar between groups. There were no intraoperative complications or conversions to open surgery in the robot-assisted group. Intraoperative blood loss was significantly higher in the transsternal group (151.43 vs. 41.67ml, P=0.01). There were 20 postoperative complications and 1 postoperative death in the transsternal group and 1 postoperative complication in the robot-assisted group (P=0.001). Hospital length of stay was 4days (range 2-27days) in the transsternal group and 1day (range 1-7days) in the robot-assisted group (P=0.002). Robot-assisted thymectomy is superior to transsternal thymectomy, reducing intraoperative blood loss, postoperative complications, and hospital length of stay. Further investigation of the long-term oncologic results in thymoma patients and long-term remission rates in patients with myasthenia gravis who underwent robot-assisted thymectomy is warranted.

Pregnancy with Myasthenia Gravis with Bad Obstetric History – A case reportPregnancy with Myasthenia Gravis with Bad Obstetric History – A case report

Myasthenia gravis is an acquired immune disorder characterized clinically by weakness and fatiguability of skeletal muscle on exertion. It is twice as common in women as in men and frequently affects women in the second and third decades of life, overlapping with the childbearing years. The incidence of myasthenia gravis with pregnancy is 1 in 20,000. Generally, during pregnancy in one third of patients the disease exacerbates whereas in two thirds it remains clinically unchanged. (1) Acetylcholine receptor (Ach R) antibodies are found in around 85% of the patients. (2) In 15% of seronegative myasthenia gravis patients without Ach R antibodies there are serum factors that increase Ach R phosphorytation and reduce Ach R function.Diagnostic test for myasthenia gravis are antibodies to Ach R ,muscle specific receptor tyrosine kinase (MuSK Ab), and striated muscle (Str Ab) ; edrophoniun test, EMG and electrophysiological tests. Supporting clinical observations include the

Thymoma: Surgical Results of 73 Cases

Purpose : Thymomas are uncommon tumours; they represent a broad spectrum of morphological and clinical behaviour. The purpose of this study is to identify the factors that influence survival.Method : Seventy-three patients with thymoma who underwent thymectomy between 1980 and 2002 were reviewed. Prognostic factors assessed were: age, sex, presenting symptoms, histological features, stage at diagnosis and extent of surgical resection.Results : Complete resection was achieved in 67 patients and incomplete in 6. Survival rates of patients in the 1st or 2nd stages were 100% and 92.8% for 10 years, respectively. A high incidence of myasthenia gravis (MG) associated thymomas (80.8%) was found. These patients had better survival rates when compared to non-myasthenic patients. However the mortality rate for malign thymomas was high (65.7%) due to tumoral invasion. The histological types of thymoma did not influence the survival rate.Conclusions : The association of MG with thymoma enables earlier detection of tumour, thus higher survival rates were achieved in these patients. Survival was also related to the stage of the tumour at diagnosis and the completeness of resection.

Mysterious falls and a nasal voice

The near-ubiquity of falls in elderly people1 should not deter doctors from seeking the cause. The annual incidence of myasthenia gravis in the UK is estimated at 1-2 in 100 000, but may be five times as high in elderly people in whom the disorder is thought to be substantially underdiagnosed. The mean time taken to diagnose myasthenia gravis in people over 60 years of age, after they develop symptoms, was estimated in 1996 as 4.5 months--almost twice the time taken to diagnose the disorder in younger people. Language: en

Formes tardives de myasthénie. Étude comparative avec la myasthénie du sujet jeune

The incidence of myasthenia gravis appears to be increasing in elderly but few studies have been devoted to late onset myasthenia gravis. We retrospectively compared myasthenic patients with an age at onset above or below 35 years which were observed in two departments of Neurology from 1980 to 2002. 81 cases were included, 28 of which were late onset myasthenia gravis. The two populations were similar in terms of sex-ratio, clinical symptoms, course of the disease and therapeutic response. There was a trend for older patients to present more frequently at onset with dysphagia and axial or proximal involvement, and to have extra-ocular symptoms more quickly. Antibodies against acetylcholine receptor and striated muscle were statistically more frequent in elder patients. A late onset is not a factor of poor prognosis in myasthenia gravis and older patients must be treated in the same way than younger ones.

Increasing incidence of late-onset anti–AChR antibody–seropositive myasthenia gravis

The incidence of myasthenia gravis (MG) from 1970 through 1999 was studied in an area with 2.3 million inhabitants. The mean annual incidence rate of early-onset MG was constant at 3.5 x 10(-6). In late-onset MG, the rate increased from 4.7 to 20.8 x 10(-6). The two onset types of MG may thus be distinct disorders. The author hypothesized that late-onset nonthymoma anti-acetylcholine receptor antibody-seropositive MG may be provoked by environmental factors.

Immunology of the neuromuscular junction and presynaptic nerve terminal.

The prevalence and incidence of myasthenia gravis is higher than previously thought. A potentially immunodominant T cell has been defined. The specific voltage-gated calcium channel subtype that is targeted by antibodies in the Lambert-Eaton myasthenic syndrome has been identified, and there is further evidence for the pathogenic role of autoantibodies in some cases of fetal arthrogryposis and in acquired neuromyotonia, Morvan's syndrome and Miller-Fisher syndrome.