Treatment of primary progressive aphasia by repetitive transcranial magnetic stimulation: a randomized, double-blind, placebo-controlled study.

To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in patients with primary progressive aphasia (PPA). In this randomized, double-blind trial in a single center, patients who were diagnosed with PPA were randomly assigned to receive either real rTMS or sham rTMS treatment. High-frequency rTMS was delivered to the dorsolateral prefrontal cortex (DLPFC). The primary outcome was the change in Boston Naming Test (BNT) score at each follow-up compared to the baseline. The secondary outcomes included change in CAL (Communicative Activity Log) and WAB (Western Aphasia Battery) compared to baseline and neuropsychological assessments. Forty patients (16 with nonfluent, 12 with semantic and 12 with logopenic variant PPA) were enrolled and randomly assigned to the rTMS or sham rTMS group, with 20 patients in each group. Thirty-five patients (87.5%) completed a 6-month follow-up. Compared to the sham rTMS group, the BNT improvement and WAB improvement in the real rTMS group were significantly higher. These significant improvements could be observed throughout the entire 6-month follow-up. At 1 month and 3 months after treatment, CAL improvements of real rTMS were significantly higher than sham rTMS. The improvements in BNT, CAL and WAB did not significantly differ among PPA variants. No significant improvement in neuropsychological assessments was observed. High-frequency rTMS delivered to DLPFC improved language functions in patients with different PPA variants. The efficacy was still observed after 6 months of treatment. Trial registration: NCT04431401 ( https://clinicaltrials.gov/ct2/show/NCT04431401 ).

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound.

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

Nerve ultrasound may help predicting response to immune treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUNDS: Nerve ultrasound has been proven to be an accurate tool in diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, its value in guiding treatment has not been well evaluated. The aim of this study was to explore whether nerve ultrasound and its changing trend could predict the response to immune treatment in CIDP. METHODS: Eighty-nine therapy-naive CIDP patients were recruited prospectively and treated with steroids and/or intravenous immunoglobulin (IVIG). Ultrasonographic and electrophysiological studies were performed on the median and ulnar nerves before treatment in all patients and followed up in 45 patients. The cross-sectional area (CSA) was measured at ten sites on both the median and ulnar nerves. RESULTS: The response rate to steroids (95%) was significantly higher than that to IVIG (70%) (P = 0.001) in patients with normal or moderately enlarged CSA, while there was no significant difference in the response rate between steroid therapy (84%) and IVIG (75%) (P = 0.653) in patients with markedly enlarged CSA. CSAs decreased in 15 patients during follow-up, most of whom had good IVIG and steroid responses (83%) and no need for immune suppressant treatment (82%). CONCLUSIONS: Nerve ultrasonography could help guide treatment strategies in patients with CIDP. Patients with normal or moderately enlarged CSA may respond better to steroids than to IVIG. The decrease in CSA after treatment may also indicate better prognosis.

Differential Expression of miRNA in the Peripheral Blood Mononuclear Cells in Myasthenia Gravis with Muscle-Specific Receptor Tyrosine Kinase Antibodies.

To determine if differential profile of miRNAs in peripheral blood mononuclear cells (PBMCs) could be identified in muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis (MuSK-MG) and linked to disease stage, a case-control method was used to compare the difference in miRNA expression profiles of PBMCs using next generation sequencing (NGS) in MuSK-MG patients and healthy controls (HCs). Six significant miRNAs from the discovery set were then validated using RT-qPCR in 11 MuSK-MG patients and 10 HCs. A unique miRNA prediction algorithm was used to predict the target genes of differentially expressed miRNAs and a network of miRNA gene pathways. Compared with HCs, 101 differentially expressed miRNAs were screened in MuSK-MG, of which 5 miRNAs were upregulated, and 96 miRNAs were downregulated. The top six differentially expressed molecules were selected for verification; four of them (miR-340-5p, miR-106b-5p, miR-27a-3p, and miR-15a-3p) were significantly different. The network analysis of miRNA gene pathways revealed that differentially expressed miRNAs were involved in a complex set of biological processes. Clinically, the four miRNAs that were validated are not correlated to MuSK antibody titers and quantitative myasthenia gravis score. Four miRNAs that were validated in this study have specificity to distinguish MuSK-MG from HCs.

Peripheral nerve hyperexcitability syndrome: A clinical, electrophysiological, and immunological study.

INTRODUCTION: Peripheral nerve hyperexcitability syndrome (PNHS) is characterized by muscle fasciculations and spasms. Nerve hyperexcitability and after-discharges can be observed in electrophysiological studies. Autoimmune mechanisms play a major role in the pathophysiology of primary PNHS. METHODS: We retrospectively conducted a case-control study recruiting patients with clinical and electrophysiological features of PNHS. Control patients were diagnosed with other neuronal or muscular diseases. Contactin-associated protein2 (CASPR2) and leucine-rich glioma-inactivated1 (LGI1) antibodies were examined. RESULTS: A total of 19 primary PNHS patients and 39 control patients were analyzed. The most common symptoms for the case group were fasciculations (11/19) and muscle spasms (13/19). Case group patients were likely to demonstrate electrodiagnostic findings of nerve hyperexcitability (17/19) and after-discharges in the tibial nerve (19/19). We found high prevalence of CASPR2 (9/19) and LGI1 (6/19) antibodies in the case group. DISCUSSION: Primary PNHS patients were likely to show after-discharges in the tibial nerve. The pathogenesis of PNHS is autoimmune CASPR2 and LGI1 antibodies are possible pathogenic antibodies for primary PNHS.

Nerve ultrasound studies in POEMS syndrome.

INTRODUCTION: The aim of our study was to assess the ultrasonographic features of peripheral nerves in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. METHOD: 34 POEMS syndrome patients and 26 healthy control (HC) participants were recruited prospectively. Cross-sectional area (CSA) was measured in nerves of limbs, trunks of brachial plexus, and cervical nerve roots RESULTS: The CSAs were mildly enlarged at the arm segment of median nerve, elbow segment of ulnar nerve and upper trunk, moderately enlarged at the forearm segment of both median and ulnar nerve, upper trunk of brachial plexus, and C6, C7 cervical nerve roots, and markedly enlarged at the arm segment of ulnar nerve, middle and lower trunk of brachial plexus, as well as C5 cervical root. DISCUSSION: The CSAs of upper limb nerves were larger in POEMS syndrome patients than in HCs, and the enlargements were most prominent proximally.

Fasciculation differences between ALS and non-ALS patients: an ultrasound study.

BACKGROUND: Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. METHODS: Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. RESULTS: The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0-3) in ALS and 0 (0-0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. DISCUSSION: The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. CONCLUSIONS: The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Abduction range: A potential parameter for the long exercise test in hypokalemic periodic paralysis during inter-attack periods.

BACKGROUND: The abduction range of the little finger in the long exercise test (ET) has rarely been reported in patients with hypokalemic periodic paralysis (HypoPP) during inter-attack periods, and the diagnostic value requires clarification. METHODS: The long ET was performed in 43 HypoPP patients during inter-attack periods and in 20 healthy controls (HCs). The compound muscle action potential (CMAP) and the abduction range of the little finger were recorded concurrently. RESULTS: There were significant differences in the percent changes of the CMAP amplitudes and the abduction ranges after exercise between HypoPP patients and the HCs. The curve of percent changes in abduction ranges overlapped substantially with that of the CMAP amplitudes, and the sensitivity, specificity, and cutoff values were 0.860, 0.900, and 22.6%, respectively. CONCLUSIONS: The abduction range of the little finger can serve as a novel parameter in the long ET for the diagnosis of HypoPP during inter-attack periods.

Whole exome sequencing identified a novel DAG1 mutation in a patient with rare, mild and late age of onset muscular dystrophy-dystroglycanopathy.

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9 (MDDGC9) is the rarest type of autosomal recessive muscular dystrophies. MDDGC9 is manifested with an early onset in childhood. Patients with MDDGC9 usually identified with defective glycosylation of DAG1, hence it is known as "dystroglycanopathies". Here, we report a Chinese pedigree presented with mild MDDGC9. The proband is a 64 years old Chinese man. In this family, both the proband and proband's younger brother have been suffering from mild and late onset MDDGC9. Muscle biopsy showed that the left deltoid muscle with an advanced stage of dystrophic change. Immunohistochemistry staining of dystrophin, α-sarcoglycan, ß-sarcoglycan and dysferlin are normal. Molecular genetic analysis of the proband has been done with whole exome sequencing. A homozygous novel missense mutation (c.2326C>T; p.R776C) in the exon 3 of the DAG1 gene has been identified in the proband. Sanger sequencing revealed that this missense mutation is co-segregated well among the affected and unaffected (carrier) family members. This mutation is not detected in 200 normal healthy control individuals. This novel homozygous missense mutation (c.2326C>T) causes substitution of arginine by cystine at the position of 776 (p.R776C) which is evolutionarily highly conserved. Immunoblotting studies revealed that a significant reduction of α-dystroglycan expression in the muscle tissue. The novelty of our study is that it is a first report of DAG1 associated muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9 (MDDGC9) with mild and late age of onset. In Chinese population this is the first report of DAG1 associated MDDGC9.

Serial nerve ultrasound and motor nerve conduction studies in chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: The objective of this study was to evaluate the correlation between cross-sectional area (CSA) and nerve conduction studies (NCS) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to determine how CSA changes over time after standard treatment. METHODS: Fifty-four patients with CIDP were recruited prospectively, and 21 patients were followed for more than 6 months. Ultrasonography and motor NCS were performed in the median and ulnar nerves. RESULTS: No or weak correlation was observed between the maximum CSA and motor conduction velocity. There were segmental nerve enlargements at 61% of sites with conduction block or temporal dispersion. Among 19 patients with clinical improvement after immunotherapy, CSA decreased to normal in 5, increased in 10, and were unchanged in 4. DISCUSSION: Different patterns of CSA and motor NCS changes after immune treatment may indicate different CIDP pathologic mechanisms. Exploration of these pathologic mechanisms could guide treatment choices in the future. Muscle Nerve, 2019.

Effects of alendronate and alfacalcidol on bone in patients with myasthenia gravis initiating glucocorticoids treatment.

OBJECTIVE: Glucocorticoids (GCs) are the first-line treatment for myasthenia gravis (MG) and act as long-term immunosuppressants. However, GCs can induce osteoporosis and bone fractures. In this study, we evaluate the effects of oral alendronate and alfacalcidol, or alfacalcidol alone on the bone of Chinese patients with MG who will initiate treatment with GCs. DESIGN AND METHODS: A total of 75 patients were included in this 12-month prospective, open-label, single-centre study. Patients with bone mineral density (BMD) T-score less than -1.0 at baseline were treated with 70 mg of alendronate per week. Patients with BMD T-score greater than -1.0 at baseline were included in the alfacalcidol-alone group. Patients in two groups were treated with 0.25 µg of alfacalcidol every other day and 600 mg of calcium daily. RESULTS: After 12 months of treatment, the mean BMD of lumbar spine, femoral neck and total hip increased by 3.4% (P = .002), 1.8% (P = .21) and 2.6% (P = .02), respectively, in alendronate group. In alfacalcidol-alone group, the mean BMD of lumbar spine, femoral neck and total hip decreased by 6.1%, 3.2% and 3.3%, respectively (all P < .001 vs baseline). CONCLUSIONS: We demonstrated for the first time that treatment with alendronate combined with alfacalcidol significantly increased BMD, decreased bone turnover biomarker levels and reduced the occurrence of hypercalciuria in a large cohort of Chinese patients with MG who initiated treatment with glucocorticoids. However, treatment with alfacalcidol alone failed to prevent bone loss in patients with MG receiving glucocorticoid therapy.

Excessive daytime sleepiness in Chinese patients with sporadic amyotrophic lateral sclerosis and its association with cognitive and behavioural impairments.

OBJECTIVE: To examine the frequency and clinical features of excessive daytime sleepiness (EDS) and its association with cognitive and behavioural impairments in patients with amyotrophic lateral sclerosis (ALS). METHODS: We conducted a cross-sectional investigation to explore the frequency and clinical features of EDS in a group of 121 Chinese patients with ALS compared with 121 age-matched and sex-matched healthy subjects. EDS was diagnosed using the Epworth Sleepiness Scale (ESS). Other characteristics of patients with ALS including sleep quality, REM sleep behaviour disorder (RBD), restless legs syndrome (RLS), cognition, behaviour, depression and anxiety were also evaluated. RESULTS: EDS was significantly more frequent in patients with ALS than in controls (26.4% vs 8.3%; p<0.05). Patients with ALS with EDS scored lower scores on the revised ALS Functional Rating Scale (ALSFRS-R), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and MMSE and MoCA delayed memory subitems and higher on the Frontal Behavioural Inventory (FBI) than patients with ALS without EDS. ESS scores correlated with global ALSFRS-R, FBI, MMSE and MoCA scores and MMSE and MoCA delayed memory scores. RLS and global ALSFRS-R scores were independently associated with EDS in patients with ALS. CONCLUSIONS: We identified a high frequency of EDS symptoms in Chinese patients with ALS, and these patients might have more serious physical, cognitive and frontal behaviour impairment. Patients with ALS might improve quality of life from the timely recognition and optimised management of EDS symptoms. Our results further suggest that ALS is a heterogeneous disease that might exhibit abnormal sleep-wake patterns.

Single-fiber EMG with concentric electrodes in lambert-eaton myasthenia.

INTRODUCTION: We analyzed jitter recordings made with concentric needle electrode (CNE) single-fiber electromyography (SFEMG) in Lambert-Eaton myasthenia (LEM). METHODS: Fifteen subjects diagnosed with LEM were studied using CNE-SFEMG in the extensor digitorum (ED) and tibialis anterior (TA) muscles. CNE-SFEMG in the ED and TA was also used to evaluate 12 and 10 healthy controls (HCs), respectively. RESULTS: Ten men and 5 women were diagnosed with LEM based on an increase of 100% in compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation. All patients exhibited markedly greater jitter in the ED (88.8 ± 23.2 µs) and TA (92.2 ± 30.2 µs) than HCs (28.3 ± 3.4 µs and 30.9 ± 5.1 µs, respectively). CONCLUSIONS: CNE-SFEMG is sensitive for discovering abnormalities in neuromuscular transmission in LEM. Muscle Nerve 56: 253-257, 2017.

Immunophenotypic and prognostic analysis of PAX8 and TTF-1 expressions in neuroendocrine carcinomas of thymic origin: A comparative study with their pulmonary counterparts.

OBJECTIVES: To investigate the immunoreactivity of TTF-1 and PAX8 in neuroendocrine carcinoma of thymic (TNEC) and pulmonary origins (PNEC), and whether their immunophenotyping could be used to distinguish between NEC of the two sites, as well as prognosis of patients with TNEC. METHODS: Twenty-two cases of TNEC and 20 cases of PNEC were selected for immunohistochemical analysis using PAX8 and TTF-1. Clinical data and follow-up information were obtained for survival analyses. RESULTS: TTF-1 immunoreactivity was seen in 19 PNEC cases (95%) and 13 TNEC cases (59.1%). PAX8 was negative in all pulmonary tumors while positive in 19 thymic cases (86.4%). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC. Survival analysis showed lung metastasis as a significant prognostic factor in TNEC. CONCLUSION: Our study demonstrated that TTF-1/PAX8 immunophenotyping may be helpful for differential diagnosis of NECs of pulmonary and thymic origins. TTF-1+/PAX8- immunophenotyping showed high specificity for PNECs, while PAX8+ alone showed a good diagnostic accuracy for TNEC. Lung metastasis was a predictive factor that associated with survival of TNEC patients. J. Surg. Oncol. 2016;114:697-702. © 2016 Wiley Periodicals, Inc.

13,14-seco-Withanolides from Physalis minima with Potential Anti-inflammatory Activity.

Four new 13,14-seco-withanolides, minisecolides A - D (1 - 4), together with three known analogues 5 - 7, were isolated from the whole plants of Physalis minima. The structures of new compounds were determined on the basis of spectroscopic analysis, including (1) H-, (13) C-NMR, 2D-NMR (HMBC, HSQC, ROESY), and HR-ESI-MS. Evaluation of all isolates for their inhibitory effects on nitric oxide (NO) production was conducted on lipopolysaccaride-activated RAW264.7 macrophages. Compounds 2, 3, 5, and 6 showed inhibitory activities, especially for compound 5 with IC50 value of 3.87 µm.

Motor nerve conduction study and muscle strength in newly diagnosed POEMS syndrome.

INTRODUCTION: Mixed demyelination and axonal loss are electrophysiological features of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. It is unclear whether the demyelination and axonal loss occur concurrently. METHODS: Electromyography was performed in 37 patients with newly diagnosed POEMS syndrome. Compound muscle action potential (CMAP) amplitude, distal motor latency, motor conduction velocity (MCV), and spontaneous activity were collected. Muscle strength was measured according to the Medical Research Council (MRC) scale. RESULTS: MCV decreased in all nerves with decreased CMAP amplitude and in 93% of nerves with normal amplitude. CMAP amplitude decreased in 54% of nerves with decreased MCV and was normal in all nerves with normal MCV. MCV deceased in 95% of nerves with normal MRC. Abnormal spontaneous activity was detected in 32% of upper limb muscles. CONCLUSIONS: Demyelination may be the main manifestation in POEMS neuropathy at an early stage, and axonal loss may be secondary to demyelination as the disease progresses.

Proteasome inhibitors for malignancy-related Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder characterized by autoantibodies against presynaptic voltage-gated calcium channels that impair neuromuscular transmission. Malignancies, especially small cell lung cancer (SCLC), have been associated with LEMS and account for approximately 60% of cases, making malignancy management a central step in LEMS therapy. In addition, immunosuppressive therapy is also recommended for symptomatic control. Interestingly, both pathological and epidemiological data suggest that the autoimmune response can inhibit progression of tumors in malignancy-associated LEMS. Thus, conventional broad-spectrum immunosuppressants may not be effective agents for treatment of LEMS, especially in those with malignancy-associated LEMS. Recent preclinical and clinical studies have indicated that proteasome inhibitors can eliminate antibody-producing cells efficiently, block dendritic cell maturation, and have anti-tumor activity. We hypothesize that proteasome inhibitors may be promising agents for treatment of malignancy-related LEMS.

[A study of autonomic dysfunction and sympathetic skin response in motor neuron disease].

OBJECTIVE: To explore the symptoms of autonomic dysfunction and sympathetic skin response (SSR) abnormality in patients of motor neuron disease (MND). METHODS: The clinical features of autonomic dysfunction were collected as follows: dermal numbness or pruritus, parahidrosis, xerostomia, salivation, abnormal skin temperature, orthostatic hypotension, mydriasis, ptosis or abnormal pupillary light reflex, constipation, voiding dysfunction and sexual dysfunction. SSR was performed and the results were judged according to the normal range of our laboratory. Abnormality rate in MND patients was calculated. The relationship between clinical symptoms and SSR parameters were analyzed statistically. RESULTS: Among a total of 142 MND patients, the symptom incidences of autonomic dysfunction were as follows: dermal numbness (53.5%), dermal pruritus (15.5%), parahidrosis (10.6%), xerostomia (9.1%), salivation (2.1%), abnormal skin temperature (14.8%), orthostatic hypotension (2.1%), constipation (16.2%), voiding dysfunction (9.9%) and sexual dysfunction (1.4%). Abnormal SSR was found in 51/142 (35.9%) patients, including 12(8.5%) in palmar and 47(33.1%) in plantar. The features of abnormal SSR included delayed latency of palmar (P < 0.05) and decreased amplitudes of both palmar and plantar compared with normal ranges (P < 0.01 respectively). The group of patients with lumbosacral onset had a higher abnormal rate of SSR than those of other onset sites. There was no significant correlation between clinical symptoms and abnormal SSR parameters. CONCLUSION: The patients of MND exhibit autonomic dysfunctions of skin, gland secretion, cardiovascular system and sphincters. Some of them show abnormal SSR with prolonged latency and decreased amplitude. The abnormalities of SSR are not related to clinical features of autonomic dysfunction. Those with an onset of lower limbs have a higher rate of abnormal SSR.

Batoclimab vs Placebo for Generalized Myasthenia Gravis: A Randomized Clinical Trial.

Importance: Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in the circulation and alleviate symptoms in patients with generalized MG. Objective: To examine the efficacy and safety profile of batoclimab, a monoclonal IgG1 antibody, in patients with generalized MG. Design, Setting, and Participants: This was a multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers in China. Adult patients 18 years or older with generalized MG were screened, and those who were antibody positive were enrolled. Intervention: Eligible patients received batoclimab or matching placebo in addition to standard of care. Each treatment cycle consisted of 6 weekly subcutaneous injections of batoclimab, 680 mg, or matching placebo followed by 4 weeks of observation. A second treatment cycle was conducted in patients who required continuing treatment. Main Outcome and Measure: The primary outcome was sustained improvement, as defined by a 3-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline for 4 or more consecutive weeks in the first cycle in individuals who were positive for acetylcholine receptor or muscle-specific kinase antibodies. Results: A total of 178 adult patients with generalized MG were screened, 132 were randomly assigned, 131 tested positive for antibodies, and 1 tested negative for antibodies. A total of 132 patients (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) were enrolled. The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). The MG-ADL score diverged between the 2 groups as early as week 2. The mean (SE) maximum difference in MG-ADL score reduction occurred 1 week after the last dose (day 43, 1.7 [0.3] in the placebo group vs 3.6 [0.3] in the batoclimab group; group difference, -1.9; 95% CI, -2.8 to -1.0; nominal P < .001). The rates of treatment-related and severe treatment-emergent adverse events in patients were 36.9% (24 of 65) and 7.7% (5 of 65) in the placebo group vs 70.1% (47 of 67) and 3.0% (2 of 67) in the batoclimab group, respectively. Conclusions and Relevance: Batoclimab increased the rate of sustained MG-ADL improvement and was well tolerated in adult patients with generalized MG. Clinical effects and the extent of IgG reduction were similar to those previously reported for efgartigimod and rozanolixizumab. Future studies of large sample size are needed to further understand the safety profile of batoclimab. Trial Registration: ClinicalTrials.gov Identifier: NCT05039190.