Despite many ALS discoveries in the past few years, scientists have yet to identify the cause of the disease. In contrast, they know what causes MG: autoantibodies binding to different elements of neuromuscular junctions. The binding leads to abnormal neuromuscular communication and consequent muscle weakness and fatigue. The Chinese team looked for studies of the two occurring at the same time, plus studies of patients who developed one disease, and then the other.
Twenty-nine cases of patients with both diseases or with one disease but symptoms of the other surfaced in a review of studies, the researchers said. And two ALS patients had myasthenia gravis symptoms but did not develop the disease.
Though manual muscle tests of the lower limbs were normal, fatigable weakness could be induced after exercise. Electromyogram EMG revealed generalized motor neuron lesion with signs of both acute and chronic denervation. A neostigmine test was positive. A computed tomography CT scan of mediastinum showed thymic hyperplasia. The patient was also found to have hyperthyroidism and was prescribed Thyrozol. His ocular symptoms and fatigable weakness improved after treatment with intravenous immunoglobulin IVIG at a dose of 0.
However, limb weakness worsened irreversibly, and dysphagia, dysarthria, and dyspnea appeared during the following year. A patient in his 50s was diagnosed with ocular MG due to fluctuating bilateral ptosis and diplopia. The symptoms went into full remission after treatment with 60 mg QD pyridostigmine bromide.
The patient was doing well without medication until 5 years later, when the ocular symptoms were aggravated, and he developed muscle weakness and wasting in bilateral lower limbs, progressively affecting all extremities and the bulbar region within 6 months. Pyridostigmine bromide 60 mg TID could partially improve the ocular symptoms, but it could not be tolerated because of generalized fasciculation. Upon examination, he had bilateral ptosis, restricted eye movements and fasciculations in the tongue.
EMG showed fibrillation potentials and positive sharp waves together with signs of chronic denervation in all extremities, the paraspinal muscles, and the sternocleidomastoid. AChR-ab was RNS, thyroid function, and CT scan of the mediastinum were all normal. He was given 0. He was diagnosed with clinically probable ALS according to the revised El Escorial World Federation of Neurology criteria 1 , and riluzole was prescribed.
Respiratory function was eventually involved, and the patient died 28 months after ALS onset. A total of articles were identified. After removing duplicate articles, the remaining articles were screened by title and abstract.
A total of 23 full-text articles were assessed for eligibility. Four studies had an obscure diagnosis of either ALS or MG or lack of important information 5 — 8 , five differentiated the two diseases but not their coexistence 9 — 13 , two reported coexistence of MG and lower motor neuron syndrome 14 , 15 , and one described an ALS patient who developed myasthenia possibly due to the use of riluzole Finally, 11 articles that reported cases diagnosed as coexistence of ALS and MG were identified 4 , 17 — A flow chart of the method of article retrieval is presented in Figure 1.
Altogether, the characteristics of 25 cases reported in the literature and 2 cases of our own were reviewed. According to their clinical course and presentation, the cases could be roughly divided into four groups Tables 1 — 3 for groups 1—3, respectively. Comparing the localization of myasthenia symptoms and the site of onset of ALS for these patients, they were always in different regions except in three cases.
Myasthenia symptoms in two patients relapsed or were aggravated concomitant with ALS symptoms, but they were sensitive to IVIG treatment. The mean survival time of seven cases was approximately 29 months. There was a profound discrepancy between their ages at onset of ALS 34—89 years old. However, most patients developed MG within the following 18 months except one.
Four patients developed the two diseases almost at the same time, and it was difficult to distinguish the order of onset. Myasthenia symptoms could be improved or relieved through immune-modulating therapy, and some recovered spontaneously. It seemed that ALS in younger patients progressed more slowly Group 4: two clinically identified ALS patients presented with fluctuating ptosis and diplopia as initial symptoms followed by dysarthria, dysphagia, and limb muscle weakness, with normal concentration of sera AChR-ab and RNS test results.
These patients were not responsive to cholinesterase inhibitors or immunosuppressive therapy Evidence was considered insufficient to make the diagnosis of MG. Herein, we presented two cases from our database and summarized the clinical characteristics of all the other cases that have been reported.
However, Turner et al. Association between two diseases may be driven by dysregulation of the immune system in both conditions. General and tissue-specific immune activation is seen in ALS Deficiency or decrease of T-regulatory cells Treg cells 29 , 30 , upregulated atrophy-related atrogenes, and neuronal nitric oxide synthase abnormalities 31 , 32 could be found in both MG and ALS.
Immunoglobulin from ALS patients can affect neuromuscular junction functional characteristics 33 , and the activity of AChRs also seems to play a role in the innervation and re-innervation of muscle fibers Experimental evidence indicates that muscle and neuromuscular junctions may be sites of disease manifestation in a very early stage of ALS By comparing the localization of myasthenia symptoms and the site of onset of ALS in Group 1, we found that they were always at different regions except in three cases.
Therefore, when muscle weakness reappeared or was aggravated in affected muscles in different regions from prior MG or was accompanied by muscle wasting, reexamination of EMG should be recommended and a possible diagnosis of ALS should be taken into consideration. The difference may come from bias due to a small number of cases. In Group 1, the mean age at onset of ALS was 71 years old, which is much older than that of patients in Group 2 mean age of 59 years old, Table 4 or general sporadic ALS patients reported mean age of 58—63 years old We speculate that immune-modulating therapy for prior MG at an early stage may have some protective or suppressive effect to delay the onset of motor neuron damage.
Immune therapy trials have been unsuccessful in ALS 39 , 40 ; however, timing is of great significance considering that ALS patients might be already in a late stage of the disease with irreparable motor neuron damage at the time of diagnosis.
She writes about medical science and drug discovery. Tags autoimmune disease , myasthenia gravis , regulatory T-cells Tregs. Recommended reading. November 11, Columns by Kristin Neva. November 11, News by Somi Igbene. November 10, Columns by Rick Jobus. Pin It on Pinterest. Treatment was started with pyridostigmine and oral prednisone, with good clinical response; at 15 months, he presented atrophy of the shoulder and pelvic girdles and right quadriceps, and exacerbation of bulbar symptoms and hyperreflexia.
The EMG revealed fasciculations and denervation potentials in the deltoids, medial head of the left gastrocnemius, and the left vastus, and in the tongue. The patient was a year-old woman with dysphonia, neurogenic dysphagia, fatigue, and exertion dyspnoea of progressive onset in the previous 2 months.
Anti-AChR antibody titre was 7. After diagnosis of class IIb MG, 3 combined treatment with pyridostigmine and prednisone was started.
Five months after onset, the patient presented anarthria. An EMG study revealed denervation activity and fasciculations in the masseter, tongue, right first interosseous muscle, abductor digiti minimi, and vastus lateralis.
The subsequent clinical progression, with lack of response to treatment with immunoglobulins and plasmapheresis, as well as the findings of the neurophysiological study, confirmed the diagnosis of definite ALS. Both processes feature an immune-mediated pathogenic mechanism. Mulder et al. This finding was associated with disease progression and predominantly affected proximal muscles frequently the trapezius in patients with ALS, whereas distal muscles showed greater involvement in MG.
When both entities coexist, MG symptoms are mainly ocular and bulbar. In these cases, immunomodulatory treatment should be considered as a diagnostic and therapeutic option.
Although the cause is unclear, this may be related to the early involvement of the neuromuscular junction, which may also explain the higher levels of anti—low-density lipoprotein receptor—related protein 4 anti-LRP4 antibodies in this disease. ISSN: Previous article Next article. Issue 8.
Pages October More article options. Letter to the Editor. Amyotrophic lateral sclerosis and myasthenia gravis overlap syndrome: 3 new cases. Download PDF. Corresponding author. This item has received. Under a Creative Commons license. Article information. Table 1. Demographic and clinical characteristics of the patients.. Full Text. Tai, L. Cui, Y. Guan, M. Liu, X.
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