Elevated serum level of interleukin-32α in the patients with myasthenia gravis

A new cytokine, interleukin-32 (IL-32), has been implicated in the pro-inflammatory immune responses in several autoimmune disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Myasthenia gravis (MG) is a well-characterized autoimmune disease directed at the postsynaptic acetylcholine receptor (AChR) or end plate of the neuromuscular junction. IL-32 is a cytokine that induces tumor necrosis factor (TNF)-α, IL-6, IL-1β, and chemokine. IL-6, TNF-α, and IL-2 are related to the pathogenesis and immunoregulation of MG. The gene expression of IL-32 is increased in human natural killer (NK) cells and T lymphocytes when stimulated by IL-2 or mitogen. NK cells influence the development of experimental autoimmune MG (EAMG) and possibly MG. The aim of this study was to examine whether IL-32α levels are increased in patients with MG and to investigate the relationship between IL-32α levels and disease activity in human MG. Serum IL-32α levels were significantly higher in the MG patients (p = 0.03): 460.07 ± 192.30 pg/mL in MG patients and 248.45 ± 188.42 pg/mL in the healthy control group. Although there was no significant statistical difference, serum IL-32α levels of patients with both anti-AChR binding and blocking antibodies trended to be higher than those without either antibodies (521.56 ± 212.92 pg/mL vs. 339.52 ± 182.78 pg/mL, p = 0.16). IL-32α serum levels tended to decrease with clinical improvement in generalized MG. This study suggests the possibility that IL-32 might contribute to MG pathogenesis or immunoregulation.     

Correlative study on the cognitive dysfunction of patients with myasthenia gravis

BACKGROUND: Myasthenia gravis (MG) is considered as a peripheral neuromuscular disorder. Some investigations demonstrate that MG affects central nervous system (CNS), and there are disorders in cognitive function, affection, sleep, mental status and others; however, there are also some different standpoints. Some questions are still disputed, such as whether or not MG exists in the CNS and cognitive function is impaired. DATA SOURCES: Using the terms of "myasthenia gravis, neuropsychological test, memory, central, brain, cognitive dysfunction and so on", we searched the Medline database for the articles about CNS involved in MG, nerve and neuropsychology as well as cognitive function, which were published in the English language between January 1985 and December 2004. Meanwhile, we also searched CNKI database by inputting "myasthenia gravis, neuropsychology and cognitive function" in Chinese for articles about involved neuropsychology and cognitive function which were published between October 1995 and June 2006 in the Chinese language. STUDY SELECTION: Data were checked in the first trial, and articles about the influences of MG on CNS, neuropsychology, cognitive function and central cholinergic function were selected, then those were obviously unrelated with above criteria were excluded. Articles which expound the influences of MG on neuropsychology and cognitive were included, but those with repeated contents were also excluded. DATA EXTRACTION: A total of 89 related English articles and 34 Chinese articles were collected, including 43 studies on involved CNS and 32 studies on involved central cholinergic function and cholinergic receptor. Sixty-three literatures were about neuropsychology and cognitive function, which were closely related with this article. Seventy-two articles met inclusive criteria and 66 were excluded. Thirty of seventy-two were chosen for analysis. DATA SYNTHESIS: MG is an autoimmune disease of muscular diseased fatigue induced by transmission blockage of acetylcholine at the peripheral neuromuscular junction. The mini-mental state examination, Wechsler memory scale, Wechsler adult intelligence scale, Boston naming test and Rey auditory verb and learning test, etc. were used in the domestic and foreign studies of cognitive function of patients with MG for detecting memory, attention, fluency of reaction as well as information-processing velocity, etc. CONCLUSION: It is thought in some investigations that disorders of memory, mental status, attention, fluency of reaction, information-processing velocity and other cognitive dysfunctions exist in patients with MG. However, there are some anti-standpoints on cognitive dysfunction caused by MG, and more work must be done for further exploration.     

Treatment of epilepsy in patients with myasthenia gravis: Is really harder than it looks?

The relationship between myasthenia gravis (MG) and epilepsy has been rarely reported. As consequence, there are no specific guidelines for the management of these conditions when they mutually occur. We reported on three patients in whom epilepsy and MG are coexisting, but in different clinical settings. Two patients were treated with antiepileptic drugs which improved their symptoms. One patient has controlled the seizures after a successful anterior temporal lobectomy with no appreciable consequences to her MG. We discuss the difficulties in the management of epilepsy in patients with MG. In addition, we report on the first epileptic surgery in a MG patient, indicating that this surgical procedure as a safe option for the treatment of intractable epilepsy in patients with MG.     

A retrospective review of 15 patients with familial myasthenia gravis over a period of 25?years

We observed, during a 25-year period, 15 patients from 6 families with autoimmune myasthenia gravis (all Chinese Han from Guangdong Province) referred to our department. Their mean onset age was 13.4 years (range 2-25 years) with 10 patients with juvenile onset. The female:male ratio was 3:2. Acetylcholine receptors antibody titers were increased in 11 patients (range 1.62-19.8 nmol/L). Thymectomy was performed in six patients, who received corticosteroids /immune inhibitor plus pyridostigmine treatments after surgery. The other patients were placed on therapy with azathioprine, cyclophosphamide, corticosteroids and acetylcholinesterase inhibitors. All patients responded well to immunosuppressants, and psychiatric symptoms were observed only in one patient who received a high dose of corticosteroids. Patients with generalized type in the same family had different presentations with variable prognosis. HLA-A 0207 was found in 9 patients (9/15), HLA-B 4601 in 11 patients (11/15), and HLA-DRB1 0901 in 12 patients (12/15). When compared to familial autoimmune myasthenia gravis in other countries, we observed peculiar characteristics of Chinese populations, such as the within-family consistency was only found in families with ocular MG type (50% of all MG families), while the pathogenetic conditions and the prognoses of the generalized MG patients may differ greatly within the same family. These findings may shed new light on the genetic predisposition and the origin of immune abnormalities of MG patients.     

Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis?

Introduction: Acetylcholine receptor (AChR) and striated muscle antibodies (StrAbs) are found frequently in myasthenia gravis (MG) patients with thymoma. In this study we aimed to determine the positive predictive value (PPV) and negative predictive value (NPV) of these antibodies for thymoma in patients with MG. Methods: Antibody findings, thymic histology, and onset age were reviewed for 1141 patients with MG. PPV and NPV of these antibodies for thymoma were determined. Results: The PPV of AChR binding antibodies plus StrAbs was highest (50.0%) with onset before the age of 40 years. The PPV of all antibodies was low (<9%) after age 40. Higher StrAb levels did not increase the PPV. The NPV of AChR binding antibodies was high (99.7%) for all ages. Conclusions: Patients without AChR binding antibody are not likely to have a thymoma. StrAbs and AChR binding antibodies are not diagnostic for thymoma, but in early‐onset MG their presence should raise the clinical suspicion for thymoma. Muscle Nerve 49 : 30–34, 2014     

Impact of myasthenia gravis on family planning: How do women with myasthenia gravis decide and why?

Introduction: We analyzed the impact of myasthenia gravis (MG) on decision‐making in family planning by women with the disease. Methods: In a cross‐sectional, anonymous survey, a standardized questionnaire was sent or handed out to 1,637 women with MG. Results: In total, 801 questionnaires were eligible for analysis. Over fifty percent of the patients had abstained from having children due to MG. The concern mentioned most often was the possible influence of MG medication on the unborn child (87.1%). Spouses/partners (91.8%) and MG treating physicians (82.9%) were the most important persons involved in the decision‐making process. Higher age and personal experience of intensive‐care treatment for MG were independently associated with the decision to abstain from having children. Lower level of knowledge was independently associated with the probability of discouraging other MG patients from having children. Conclusions: Women with MG need specific guidance about family planning issues, which may lead to lower rates of voluntary childlessness. On the basis of our data, more specific hypotheses can be generated that require prospective investigation. Muscle Nerve 52:371–379, 2015     

Is exercise necessary with repetitive nerve stimulation in evaluating patients with suspected myasthenia gravis?

We retrospectively evaluated the effect of exercise on the degree of decrement in ulnar, spinal accessory, and facial repetitive nerve stimulation (RNS) in 179 patients with myasthenia gravis (MG) to assess whether exercise increases the diagnostic yield of identifying significant decrements. The mean worsening of decrement following exercise was 1.9% (ulnar nerve), 1.9% (spinal accessory nerve), and 1.3% (facial nerve). Abnormal (> or =10%) decrement solely following exercise occurred in the ulnar nerve in 7% of patients, accessory nerve in 5%, and facial nerve in 7%. When analyzed according to Myasthenia Gravis Foundation of America class of disease, the likelihood of producing > or =10% decrement only after exercise was greatest in class I MG with facial RNS and in class II and III generalized MG with ulnar and spinal accessory RNS. In all other disease stages, the likelihood of producing > or =10% decrement only after exercise was < or =7%. This study suggests that exercise increases the yield of diagnosis of MG by RNS in only a small percent of patients. Therefore, in most patients with suspected MG, RNS at rest is sufficient and the additional time required for prolonged postexercise RNS may be better spent in examining other muscle-nerve combinations.     

A portrait of myasthenia gravis?

The paper presents a work of art showing a presumably myasthenic patient painted more than 50 years before the disease was first described.     

Sympathetic skin response in patients with myasthenia gravis★ A comparative analysis

BACKGROUND: The examination of sympathetic skin response is an important index for assessing the autonomic nerve function, and patients with myasthenia gravis are always accompanied by dysautonomia. Therefore, it will be important to know whether sympathetic skin response can be used as the index for the clinical evaluation of myasthenia gravis. OBJECTIVE: To investigate the diagnostic value of sympathetic skin response in the damage of autonomic nerve function of patients with myasthenia gravis. DESIGN: A case-controlled comparative observation. SETTING: Department of Neurology and Room of Nerve Electromyogram, the Affiliated Hospital of North Sichuan Medical College. PARTICIPANTS: Thirty outpatients or inpatients with myasthenia gravis were selected from the Department of Neurology, the Affiliated Hospital of North Sichuan Medical College from May 2006 to May 2007, including 9 males and 21 females, aged 8–72 years with a mean age of (28±5) years old. They were all accorded with the diagnostic standards of myasthenia gravis, accompanied by different severity of autonomic nerve symptoms, including poor skin nutrition, sweating of hands and feet, pyknocardia, persistent hypotension, abdominal pain, constipation, etc. They all had not taken any drug affecting the autonomic nerve function before the examination. Informed consents were obtained from all the patients. Meanwhile, 30 healthy physical examinees were enrolled as the normal control group, including 10 males and 20 females, aged 10–75 years with a mean age of (31±5) years old. Approval was obtained from the hospital ethic committee. METHODS: After admission, the patients were examined with sympathetic skin response using DANTEC keypoint 2.0 electromyography evoked potential apparatus (Danmark). The changes of the latency and wave amplitude of sympathetic skin response were observed. The subjects in the normal control group were examined with the same methods at physical examination. Abnormality was judged by the disappearance of wave form, latency longer than that in the normal control group by Mean±2.5SD, or wave amplitude lower than the average value in the normal control group by 50%. MAIN OUTCOME MEASURES: The results of the latency and wave amplitude of sympathetic skin response were compared between the patients with myasthenia gravis and normal controls. RESULTS: All the 30 patients with myasthenia gravis and 30 healthy physical examinees were involved in the final analysis of results. There were no significant differences between the left and right upper and lower limbs in both the myasthenia gravis group and normal control group (P > 0.05). In the myasthenia gravis group, the abnormal rate of sympathetic skin response was 37% (11/30), the latency was prolonged and the wave amplitude was decreased as compared with those in the normal control group, and there were significant differences (P < 0.01). CONCLUSION: Sympathetic skin response can be used as an electrophysiological index for judging the damages of autonomic nerve function in patients with myasthenia gravis.     

Acetylcholine receptor antibody positivity rate in ocular myasthenia gravis: a matter of age?

Journal of Neurology - Anti-acetylcholine receptor antibodies (AChR Abs) are detected in 85% of myasthenia gravis (MG) patients, at higher rates in patients with late-onset disease. AChR Ab...     

Association between musk antibody concentrations and the myasthenia gravis composite score in 3 patients: A marker of relapse?

Introduction: Muscle-specific tyrosine kinase (MuSK) autoantibody related myasthenia gravis is characterized by bulbar and respiratory manifestations, a poor response to anticholinergics, and a generally good response to plasma exchange and rituximab. It is not known if MuSK-antibody (Ab) levels could be used to predict the clinical course Methods: Three patients for whom frequent long-term monitoring of MuSK-Ab levels and the Myasthenia Gravis Composite (MGC) scores were performed are described. Results: A close relationship existed between the MuSK-Ab concentrations and the MGC score. Furthermore, a rise in Ab concentration preceded a more serious clinical relapse in all patients Conclusions: These findings suggest that MuSK-Ab concentrations may be a useful biomarker for the long-term monitoring of MuSK myasthenia gravis, particularly while in clinical remission. This may allow preemptive escalation of therapy to prevent clinical relapse, and conversely permitting greater weaning of unnecessary immunosuppression. Muscle Nerve, 2019     

Correlation of bite force with excitation–contraction coupling time of the masseter in myasthenia gravis

ObjectiveThe aim of this study was to elucidate the relationship between the impairment of excitation–contraction (E–C) coupling of masseter and the bite force in patients with myasthenia gravis (MG).MethodsIn 20 patients with MG, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRP) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E–C coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT, and bite force were performed before and after corticosteroid therapy alone or in various combinations with FK506, cyclosporin A, intravenous immunoglobulin and immunoabsorption.ResultsPercent amplitude decrement in RNS and ECCT decreased significantly accompanying an increase in bite force after treatment. Simple regression analysis demonstrated a linear correlation among % decrement, ECCT and bite force. However, ECCT shortening accompanying bite force recovery without reduction in % decrement was observed in 4 patients.ConclusionsMasseteric E–C coupling is impaired in some MG patients, and functional recovery of E–C coupling contributes at least in part to the increase in bite force after treatment.SignificanceImpaired E–C coupling contributes to muscle weakness in patients with MG.     

What's in a smile? Neural correlates of facial embodiment during social interaction

Previous investigations have shown that the perception of socially relevant facial expressions, indicating someone else's intention to communicate (e.g., smiling), correlate with increased activity in zygomaticus major muscle regardless of whether the facial expressions seen are directed towards the human observer or toward someone else (Mojzisch et al., 2006). These spontaneous, involuntary reactions have been described as facial mimicry and seem to be of considerable importance for successful interpersonal communication. We investigated whether specific neural substrates underlie these responses by performing a finite impulse response (FIR) analysis of an experiment using functional magnetic resonance imaging (fMRI) to investigate the perception of socially relevant facial expressions (Schilbach et al., 2006). This analysis demonstrates that differential neural activity can be detected relative to the FIR time window in which facial mimicry occurs. The neural network found includes but extends beyond classical motor regions (face motor area) recruiting brain regions known to be involved in social cognition. This network is proposed to subserve the integration of emotional and action-related processes as part of a pre-reflective, embodied reaction to the perception of socially relevant facial expressions as well as a reflective representation of self and other.     

What's in a smile? Neural correlates of facial embodiment during social interaction

Abstract

Previous investigations have shown that the perception of socially relevant facial expressions, indicating someone else's intention to communicate (e.g., smiling), correlate with increased activity in zygomaticus major muscle regardless of whether the facial expressions seen are directed towards the human observer or toward someone else (Mojzisch et al., 2006). These spontaneous, involuntary reactions have been described as facial mimicry and seem to be of considerable importance for successful interpersonal communication. We investigated whether specific neural substrates underlie these responses by performing a finite impulse response (FIR) analysis of an experiment using functional magnetic resonance imaging (fMRI) to investigate the perception of socially relevant facial expressions (Schilbach et al., 2006). This analysis demonstrates that differential neural activity can be detected relative to the FIR time window in which facial mimicry occurs. The neural network found includes but extends beyond classical motor regions (face motor area) recruiting brain regions known to be involved in social cognition. This network is proposed to subserve the integration of emotional and action-related processes as part of a pre-reflective, embodied reaction to the perception of socially relevant facial expressions as well as a reflective representation of self and other.     

β2-Adrenergic receptor gene polymorphisms in the relapse of myasthenia gravis with thymus abnormality

Background. The role of β2-adrenergic receptor (β2-AR) in the relapse of myasthenia gravis (MG) associated with thymus abnormality has not been fully identified. Methods. Using polymerase chain reaction and gene sequencing method, we investigated the relationship of β2-AR gene polymorphisms with different thymus pathology in MG patients. The role of β2-AR gene polymorphisms in the relapse of MG was further investigated. Results. Age of onset (p = 0.034), the onset symptom of ocular MG (OMG; p = 0.023), the first symptom of OMG second generalization (p = 0.040) were different in MG with thymoma from those in MG with normal thymus or thymus hyperplasia. Gene polymorphisms of β2-AR on positions 16 and 27 showed no significant difference between relapsed and non-relapsed MG patients with thymus abnormality (thymus hyperplasia: position 16, p = 0.792; position 27, p = 0.664; thymoma: position 16, p = 0.226; position 27, p = 0.615). However, genotypes distribution on position 27 among MG patients with three thymus histology was significantly different (χ² = 8.153, p = 0.041). Furthermore, glucocorticoid can decrease relapse of MG with thymus hyperplasia (p = 0.021). Conclusions. MG patients with thymus abnormality differ from MG patients with normal thymus in age of onset, the onset symptom of OMG and the first symptom of OMG second generalization. β2-AR gene polymorphisms had no relationship with the relapse of MG with thymus abnormality. Gene polymorphism of β2-AR on position 27 was associated with different thymus histology of MG. Glucocorticoid was able to reduce the risk of relapse of MG with thymus hyperplasia.     

What have we learned about cognition in myasthenia gravis?: a review of methods and results

Most individuals with myasthenia gravis (MG) complain of cognitive impairment, but empirical studies of cognition in MG have produced mixed results. In the present review, we critically examined the methodology and results of previous studies that investigated cognition in MG. Results from our review revealed that none of the studies met at least 50% of criteria under review. The most common shortcomings of previous studies included small sample size, no exclusion for visual difficulties in patients, inadequate assessment of mood, and poor control for prednisone use. Despite these methodological difficulties, mild impairments on measures of learning have been identified. These findings need to be replicated with adequate control of potential confounds before any conclusions can be made regarding cognition in this disease. Suggestions for design of future studies are provided.