MYASTHENIA GRAVIS PDF
Synonyms: Myasthenia gravis (juvenile and adult form) autoimmune Myasthenia gravis (MG) is an autoimmune disorder with increasing frequency and. What Is Myasthenia Gravis? Myasthenia gravis (MG) is a neuromuscular disorder that causes muscle weakness. It affects muscles that a person can usually. Myasthenia gravis is the prototype neuromuscular disease with immunological pathogenesis. The Myasthenia gravis (MG) is an important neuromuscular.
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Myasthenia Gravis (MG), Lambert-Eaton Myasthenic Syndrome (LES) & Myasthenia gravis (MG) causes weakness that gets worse with exertion and improves. Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, antibody-negative, and ocular forms of myasthenia gravis. Myasthenia gravis is an autoimmune disease in which anti- new diagnostic tests for myasthenia gravis, updated treatment algorithms, and.
A lumbar puncture was performed which revealed an absence of cells with normal protein and glucose the fluid culture that ensued was negative. Vegetations were not observed. A computed tomography of the thorax and upper and lower abdomen was performed which did not reveal any significant findings. Thyroid function tests were within normal range. Complement factors C3 and C4 were elevated.
Repeated blood and urine cultures were negative. The Mantoux screening test was negative. A gastroscopy and colonoscopy were performed which were normal.
Due to the low-grade fever which persisted and the elevated inflammatory markers, despite the absence of other signs or symptoms of infection, broad spectrum antibiotics were initiated, as was antiplatelet therapy clopidogrel. The low-grade fever and inflammatory markers persisted despite the antibiotic regime. She also mentioned deterioration in her vision, which was objectively confirmed with reduced optical acuity and a limitation in the visual fields completely in the right eye.
Magnetic resonance imaging MRI of brain confirmed the CT findings without revealing significant additional pathologic features. Due to the reduced optical acuity and the limitation in the visual fields—although the full clinical picture of the patient could not be interpreted by a probable diagnosis of giant cell arteritis—a temporal artery biopsy as well as skin, muscle, and vessel biopsy was performed.
Histological examination indeed confirmed giant cell arteritis, while the AChR-Ab were also positive Figure 1.
The skin muscle vessel biopsy did not reveal any pathology. Figure 1: Destruction of the wall by an inflammatory infiltrate containing multinucleated giant cells associated with the internal elastic lamina of the artery Hematoxylin-Eosin The dysphagia, dysarthria, and blepharoptosis showed immediate response to the steroid treatment.
Patient was discharged with high-dose oral steroids prednisolone 55 mg daily , oral pyridostigmine 60 mg three times daily , and antiplatelet therapy. Four weeks after she was discharged from our department, the patient presented to the emergency room with dyspnea and palpitations.
Upon physical examination, except for tachypnea and tachycardia, an edema of her right leg was noted. ECG showed a sinus tachycardia. She had respiratory alkalosis and elevated D-dimers levels. Deep vein thrombosis was probably the result of the limited mobility of the patient due to myasthenia, as the evaluation for thrombophilia was unrevealing. Discussion This case presents clinical interest because it involves the diagnosis of two independent chronic diseases in a patient hospitalized for stroke.
Several clinical observations support the idea that a general derangement of the immune system regulation plays an important role in the pathophysiology of MG. Finally, patients with MG demonstrate a therapeutic response to various immunomodulating therapies, immunosuppressants, and thymectomy [ 8 ]. These observations suggest that common mechanisms may exist which predispose MG patients for additional autoimmune disorders.
An extensive review of the literature revealed very few cases of the coexistence of MG and vasculitis. In a more recently published study by Liozon et al.
Myasthenia Gravis and Stroke in the Setting of Giant Cell Arteritis
We also found one case report describing the concurrence of MG with polyarteritis nodosa [ 11 ], as well as a case of myasthenia gravis in the setting of microscopic polyangiitis [ 12 ]. In our patient, as was presented in the brief history, there was a time coincidence of the clinical manifestation of the two diseases.
The persistent fever, headache, and especially the decrease in optical acuity demanded that the diagnostic followup includes GCA. Nevertheless, solely this diagnosis was not adequate to interpret the entire clinical picture. The blepharoptosis was unilateral in the beginning, which is quite unusual in MG [ 13 ].
This is why the suspicion of MG intensified when during her hospitalization bilateral blepharoptosis, dysphagia, and proximal muscle weakness were added to the clinical picture. It is worth noting that our patient presented to the ER and was initially hospitalized due to symptoms of left pyramidal syndrome which were found to be caused by an ischemic brain infarct. We speculate that the stress of the stroke led to an exasperation of the symptoms of MG in our patient.
We consider the stroke to be associated with the history of arterial hypertension. It is important to add that there are very few cases of concomitant stroke and GCA in the literature. This can be explained by the fact that the inflammatory response in GCA is directed towards the elastic fibres in the media and adventia, which are sharply reduced within about 5 mm of the artery entering the dura. GCA is reportedly the cause of first-ever stroke in only 0.
Conclusion Myasthenia gravis has been associated with a number of autoimmune disorders; we report a rare case of its coexistence with giant cell arteritis.
The diagnosis of GCA can prove to be very challenging especially in the case of the coexistence of a second newly diagnosed disease such as MG. Moreover, clinicians should keep in mind that MG may occur in the setting of other autoimmune diseases. It is of special significance to note how vigilant clinicians must be in rapidly considering the possibility of MG but mainly GCA, especially when it presents with visual disturbances.
Conflict of Interests The authors declared that they have no conflict of interests.
References V. Juel and J. Salvarani, F. Cantini, and G. Wilkinson and R. Brogger Christensen, T. Jensen, I. Tsiropoulos et al. Toth, D. McDonald, J. Oger, and K. Vaiopoulos, P.
Sfikakis, V. In , Blalock reported improvement in myasthenic patients after thymectomy. Following these discoveries, cholinesterase inhibitor therapy and thymectomy became standard and accepted forms of treatment for MG [ 12 ]. In , Nastuk et al.
In the s prednisone and azathioprine were introduced as treatment modalities for MG followed by plasma exchange that was introduced for acute treatment of severe MG, all supporting the autoimmune etiology [ 16 ]. Thymoma-associated MG may also have additional paraneoplasia-associated antibodies e. They have atypical clinical features like selective facial, bulbar, neck, or respiratory muscle weakness with occasional marked muscle atrophy and with relative sparing of the ocular muscles.
Respiratory crises are more common with involvement of muscle groups like paraspinal and upper esophageal muscles. Enhanced sensitivity, nonresponsiveness, or even clinical worsening to anticholinesterase medications has also been reported.
Disease onset is earlier with female predominance and thymus histology is usually normal [ 20 ]. Seronegative MG lacks both anti-AChR and anti-MuSK antibodies and forms a clinically heterogenous group with purely ocular, mild generalized, or severe generalized disease.
Some patients may have low-affinity anti-AChR antibodies, nondetectable by current assays.
They are essentially indistinguishable from patients with anti-AChR antibodies in terms of clinical features, pharmacological treatment response, and possibly even thymic abnormalities [ 21 , 22 ].
Thymomas are frequently associated with autoimmunity.
Neoplastic epithelial cells in thymomas express numerous self-like antigens including AChR-like, titin-like, and ryanodine-receptor-like epitopes [ 19 , 23 ]. These antibodies react with epitopes on the muscle proteins titin and ryanodine receptor, are found mainly in association with thymoma and late-onset myasthenia gravis, and may correlate with myasthenia gravis severity.
These striational antibodies are principally detected only in the sera of patients with MG and rarely found in AChR antibody-negative MG.
Myasthenia Gravis: A Review
The frequencies of striational antibodies in thymoma-associated MG patients are high. Since the presence of striational autoantibodies is associated with a more severe disease in all MG subgroups, these antibodies can therefore be used as prognostic determinants in MG patients [ 25 ].
Neurophysiological examination with repetitive nerve stimulation and jitter measurements are important in establishing the initial diagnosis, especially in patients without detectable antibodies [ 16 ]. It is designed to identify subgroups of patients with MG who share distinct clinical features or severity of disease that may indicate different prognoses or responses to therapy.
It should not be used to measure outcome and is as follows.
Class I MG is characterized by the following: any ocular muscle weakness. Class II MG is characterized by the following: mild weakness affecting muscles other than ocular muscles, may also have ocular muscle weakness of any severity. Class IIa MG is characterized by the following: predominantly affecting limb, axial muscles, or both may also have lesser involvement of oropharyngeal muscles. Class IIb MG is characterized by the following: predominantly affecting oropharyngeal, respiratory muscles, or both, may also have lesser or equal involvement of limb, axial muscles, or both.
Class III MG is characterized by the following: moderate weakness affecting muscles other than ocular muscles, may also have ocular muscle weakness of any severity. Class IIIa MG is characterized by the following: predominantly affecting limb, axial muscles, or both, may also have lesser involvement of oropharyngeal muscles. Class IIIb MG is characterized by the following: predominantly affecting oropharyngeal, respiratory muscles, or both, may also have lesser or equal involvement of limb, axial muscles, or both.
Class IV MG is characterized by the following: severe weakness affecting muscles other than ocular muscles, may also have ocular muscle weakness of any severity. Class IVa MG is characterized by the following: predominantly affecting limb, axial muscles, or both, may also have lesser involvement of oropharyngeal muscles. Class IVb MG is characterized by the following: predominantly affecting oropharyngeal, respiratory muscles or both, may also have lesser or equal involvement of limb, axial muscles, or both.
Class V MG is characterized by the following: intubation with or without mechanical ventilation, except when employed during routine postoperative management, the use of feeding tube without intubation places the patient in class IVb. The NMJ postsynaptic membrane has deep folds with acetylcholine receptors AChR tightly packed on the top of these folds.
When the nerve action potential reaches the synaptic bouton, depolarization opens voltage gated Calcium channels on the presynaptic membrane, triggering release of ACh into the synaptic cleft. The ACh diffuses into the synaptic cleft to reach postsynaptic membrane receptors where it triggers off the end-plate potential EPP and gets hydrolyzed by AChE within the synaptic cleft. MuSK muscle specific tyrosine kinase , a postsynaptic transmembrane protein, forms part of the receptor for agrin, a protein present on synaptic basal lamina.
Rapsyn, a peripheral membrane protein on the postsynaptic membrane, is necessary for the clustering of AChR. NMJ findings that influence susceptibility to muscle weakness and MG: EPP generated in normal NMJ is larger than the threshold needed to generate the postsynaptic action potential by a measure of multiple folds.
Reduction in number or activity of the AChR molecules at the NMJ decreases the EPP, which may be adequate at rest; but when the quantal release of ACh is reduced after repetitive activity, the EPP may fall below the threshold needed to trigger the action potential [ 29 ]. This translates as clinical muscle weakness, and when EPP, at rest is consistently below the action potential threshold, it leads to persistent weakness. Th2 cells secrete anti-inflammatory cytokines, like IL-4, IL-6, and IL, which are important inducers of humoral immune responses.
Th1 cells are indispensible in the development of EAMG as proven in animal models.
Tregs in MG patients may be functionally impaired and are shown to increase after thymectomy with correlated symptom improvement. MG patients have been shown to have increased serum level of IL, which tends to decrease with clinical improvement [ 35 ].
Other ethnic groups or locations e. Some human muscle cell culture studies have shown cell cycle arrest, downregulation of AChR subunit with rapsyn, and other muscle protein expression, on exposure to sera from anti-MuSK-positive MG patients [ 2 ]. Other antimuscle cell protein antibodies e.Indeed, most patients require life-long immunosuppressive treatment which favors opportunistic infections, lymphoma and other severe treatment-associated side effects.
Patients must be connected to cardiac and blood pressure monitors prior to injection because of possible risk of arrhythmia and hypotension. The benefit of thymectomy evolves over several years. When the nerve action potential reaches the synaptic bouton, depolarization opens voltage gated Calcium channels on the presynaptic membrane, triggering release of ACh into the synaptic cleft. Self-tolerant T cells continue their differentiation and finally become exported to the periphery.
It allows simultaneous recording of the action potentials of two muscle fibers innervated by the same motor axon. Rapsyn, a peripheral membrane protein on the postsynaptic membrane, is necessary for the clustering of AChR. Histological examination indeed confirmed giant cell arteritis, while the AChR-Ab were also positive Figure 1. Active physical training should be encouraged.