The first patient we described was AChR-ab and MUsK-ab unfavorable, but we did not test for LRP4 antibodies. patients with false-positive anti-acetylcholine receptor, and the other 2 ALS patients with only myasthenia symptoms. Most patients experienced limb onset ALS, and myasthenia symptoms mainly affected ocular and bulbar muscles. Clinical and neurophysiological characteristics were summarized. Conclusion These findings support the conclusion that immunological mechanisms and alterations in the neuromuscular junction are related to ALS pathogenesis. (%)8/12 (67%)5/7 (71%)13/19 (68%)Bulbar, (%)4/12 (33%)2/7 (29%)6/19 (32%)Localization of MG symptomsOcular, (%)10/12 (83%)7/8 (88%)17/20 (85%)Bulbar, (%)6/12 (50%)5/8 (63%)11/20 (55%)Limbs, (%)4/12 (33%)0/8 (0%)4/20 (20%) Open in a separate window Group 2 contained patients diagnosed with ALS as the inaugural disease followed by MG (details in Tables ?Tables22 and ?and4),4), including eight patients (male:female?=?6:2). There was a profound discrepancy between their ages at onset of ALS (34C89?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. As in Group 1, most cases (5/7) were limb onset ALS, and myasthenia symptoms only affected ocular and bulbar muscles. In addition to the most common AChR-ab associated MG in six patients, the other two patients were positive for LRP4-ab (24). 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 (22). Table 2 Patients with ALS as inaugural disease followed by MG. thead th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Patients /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Nationality /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ ALS classification /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Site of onset of ALS /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Regions of EMG neurogenic pattern /th th valign=”top” align=”center” rowspan=”1″ Imatinib Mesylate colspan=”1″ Interval time between two disease /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Localization of myasthenia symptoms /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Neostigmine test /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ AChR-ab (nmol/l) /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ RNS CMAP decrement (%) /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ CT scan of mediastinum /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Associated immune-mediated disease /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Immune-directed therapy /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Effect on myasthenia symptoms /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Riluzole /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Prognosis (worsened or Died/survival) /th /thead 1 (22)FrenchDefiniteUL distalUL/LL/bulbar5?yearsOcular, head drop+AChR-ab 5.9 ( em N /em ? ?0.5) 10NormalNoNoImproveYesStable in 1?year2 (22)FrenchProbableBulbarUL/LL18?monthsOcular+AChR-ab 10 ( em N /em ? ?2)12C16NormalNoNoSpontaneous remissionYesProgress very slowly in 15?years3 (22)FrenchProbableLL distalUL/LL6?monthsBulbar, head drop+AChR-ab? ?100 ( em N /em ? ?0.5)13C50NANoIVIG, corticosteroidsCompletely recoveredYesWorsened quickly4Case 1ChineseProbable-lab supportedUL proximalUL/LL/bulbar/paraspinal5?monthsOcular+AChR-ab 1.0 ( em N /em ? ?1.1)38Thymic hyperplasiaHyperthyroidismCorticosteroids, IVIGSignificantly improvedNoWorsened slowly5 (23)NorwayProbableLimbUL/LL/bulbar0Ocular+AChR-ab 1640NormalNoPlasmapheresis, corticosteroid, azathioprineImprovedNADied/16 mo6 (26)CaucasianDefiniteNANA0Ocular, bulbarNAPositive 10NANoIVIG, prednisoneImprovedNAWorsened7 (24)JapaneseProbableBulbarUL/LL/bulbar0Ocular, bulbar+Anti-LRP4 1.08 ( em N /em ? ?1.0)NormalNormalNoSteroid, IVIG, plasmapheresisImproved partiallyNAWorsened8 (24)JapaneseProbableUL distalUL/LL/bulbar/paraspinal0Ocular, head drop+Anti-LRP4 1.5 ( em N /em ? ?1.0)10.6NANoSteroid, plasmapheresisImprovedNADied/16?months Open in a separate window em UL, upper limb, LL, lower limb, NA, not applied, CMAP, compound muscle action potential, EMG, electromyogram, IVIG, intravenous immunoglobulin; ALS, amyotrophic lateral sclerosis; MG, myasthenia gravis; AChR-ab, acetylcholine receptor antibodies; RNS, repetitive nerve stimulation; CT, computed tomography /em . Group 3 contained five ALS patients (female:male?=?3:2; age at onset of ALS: 37C88?years old) who were only positive for AChR-ab in sera (Table ?(Table3)3) but did not have any other characteristics of MG, including fluctuating symptoms, abnormal RNS test, or response to cholinesterase inhibitors. We characterize these patients as having ALS with false-positive AChR-ab as in previous papers (17). 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 Imatinib Mesylate not responsive to cholinesterase inhibitors or immunosuppressive therapy (18). Evidence was considered insufficient to make the diagnosis Imatinib Mesylate of MG. Discussion Herein, we presented two cases from our database and summarized the clinical characteristics of all the other cases that have been reported. Coexistence of ALS and MG is rare. However, Turner et al. (27) found that there were significantly more cases of ALS associated with a prior autoimmune disease, including MG. 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 (28). 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 (28). Experimental evidence indicates that muscle and neuromuscular junctions may be sites of disease manifestation in a very early NPM1 stage of ALS (34). According to the dying-back hypothesis, it is possible that neuromuscular transmission failure and postsynaptic membrane damage in MG patients may precede lower and upper motor neuron loss, thereby increasing the probability of developing ALS (28). For patients who.