Objective:To analyze the clinical characteristics and prognosis of patients with stiff-person syndrome (SPS) associated with glutamic acid decarboxylase (GAD) antibodies.Methods:A retrospective analysis was conducted on demographic characteristics, clinical manifestations, auxiliary examination results, treatment, and prognosis of patients with GAD antibody-related SPS treated at Peking Union Medical College Hospital from January 2015 to July 2023.Results:A total of 33 patients were included, comprising 26 females (78.8%) and 7 males (21.2%), with an onset age of (42±12) years and a disease duration of 24.0 (10.5, 37.5) months. Two cases (6.1%) were diagnosed with tumors, including 1 case with invasive thymoma and 1 case with small cell lung cancer. The majority of patients (87.9%, 29/33) presented with stiffness of trunk and proximal limb muscles, 42.4% (14/33) of patients exhibited episodic spasm, and 54.5% (18/33) of patients were triggered by stimuli such as sound and light. Babinski or Chaddock reflexes were elicited in 33.3% (11/33) of patients. Some patients (36.4%, 16/33) had concurrent limbic encephalitis/epilepsy or cerebellar ataxia (referred to as complex SPS). The median cerebrospinal fluid (CSF) white blood cell count was 2×10 6/L [quartile: 1×10 6/L, 6×10 6/L; range: (0-30)×10 6/L], with mild elevation in 28.0% (7/25) of patients. Multi-channel surface electromyography in 14 out of 21 cases (66.7%) suggested synchronous contraction of agonist and antagonist muscles in a relaxed state. The modified Rankin Scale (mRS) score during the acute phase was 4 (3, 4). All patients received treatment with benzodiazepines or baclofen. Thirty patients (90.9%, 30/33) received first-line immunotherapy, 3 patients (9.1%, 3/33) received second-line immunotherapy with rituximab, and 14 (42.4%, 14/33) received mycophenolate mofetil as long-term immunotherapy. The follow-up period was 16 (10, 42) months, with a median best mRS score of 2; 66.7% (22/33) of patients had a favorable functional prognosis (mRS score≤2), and the recurrence rate was 30.0% (9/30). At the last follow-up, the median mRS score was 2, and 53.3% (16/30) of patients had a favorable functional prognosis. Prognosis was not significantly correlated with gender, age, clinical type, or CSF white blood cell level (all P>0.05). Conclusions:SPS is one of the main clinical phenotypes of GAD antibody-related neuroimmune diseases, commonly observed in middle-aged women, and exhibits a chronic progressive course. Only a minority of patients have concomitant tumors. The diagnosis relies on typical symptoms, GAD antibody testing, and electromyography examination. The initial immune therapy yields good results, but the prognosis for recurrent patients is poor.

POEMS syndrome is a rare paraneoplastic syndrome due to plasma cell neoplasm. It is a disorder involving multiple organs, mainly manifesting as demyelinating peripheral neuropathy. The major diagnostic criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder, sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. A good history and physical examination followed by appropriate testing-radiographic assessment of bones, measurement of vascular endothelial growth factor, bone marrow biopsy and electromyography can differentiate this syndrome from other conditions such as chronic inflammatory demyelinating polyradiculoneuropathy, other plasma disorders (including amyloidosis, myeloma, and monoclonal gammopathy of undetermined significance neuropathy). Early diagnosis and treatment could greatly improve the prognosis.

Objective:To investigate the clinical and electrophysiological characteristics of facial onset sensory motor neuronopathy (FOSMN) syndrome.Methods:Ten patients diagnosed with FOSMN syndrome in Peking Union Medical College Hospital from January 2012 to December 2022 were included. The clinical and electrophysiological characteristics of patients were analyzed and summarized, and the genetic testing was also performed in these patients.Results:The age of onset was (56.6±6.5) years, and the longest survival duration of disease was 10 years. All patients had numbness around the face and mouth as the first symptom and abnormal blink reflex. A total of 52 sensory nerve conduction nerves were detected, among which 2 median nerves and 2 μlnar nerves showed decreased amplitude of sensory nerve action potential. Needle electromyography showed neurogenic lesions, with both progressive and chronic denervation. Whole exome sequencing identified the heterozygous variant c.272A>C in the exon 4 of the SOD1 gene resulting in the amino acid change p.Asp90Ala in 1 patient. In all patients, the disease progressed relentlessly and eventually led to involvement of respiratory muscle. Conclusion:FOSMN syndrome is characterized by abnormal blink reflex and sometimes abnormal sensory nerve conduction may be shown on electrophysiologic testing.

Objective:To report the clinical characteristics of a case of childhood amyotrophic lateral sclerosis (ALS) caused by SPTLC2 c.778G>A (p.Glu260Lys) mutation. Methods:Whole exon sequencing or whole genome sequencing data from 1 936 patients in the ALS cohort of Peking Union Medical College Hospital were screened for SPTLC2 gene mutations. Clinical data, laboratory examination, neurophysiological examination and genetic test results of the proband were collected. Results:Only one 9-year-old male child with SPLTC2 gene mutation was found. He was admitted to the Department of Neurology, Peking Union Medical College Hospital in December 2022 due to"progressive limb weakness for more than 4 years". Physical examination revealed atrophy and fasciculations of the tongue. Weakness of 4 limbs, muscle atrophy, as well as bilateral hyperreflexia, clonus, and Babinski sign were present. Whole genome sequencing indicated that SPTLC2 gene had c.778G>A (p.Glu260Lys) missense mutation, and no other pathogenic mutations of ALS related genes were detected. Sanger sequencing and family verification showed that neither father nor mother carried the mutation, suggesting that it was a de novo mutation. Nerve conduction velocity test showed no abnormalities, and electromyography suggested neurogenic lesions. Neurofilament light chain in cerebrospinal fluid and serum were increased significantly. The patient′s symptoms continued worsening even after oral administration of L-serine. Conclusion:SPTLC2 gene mutation can cause childhood ALS, and further study of its potential pathogenesis is helpful to uncover another potential pathway of ALS and a novel therapeutic target.

The complement system is a self-protection mechanism of the human body. The abnormal activation of the complement system is involved in the occurrence and development of various diseases. The application of complement inhibitors in many rare diseases was a milestone in leading to the progress of such disease as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and others. Recently, the application of complement inhibitors has gradually expanded to other complement-related diseases. This review summarizes the literature on the current application of complement inhibitors in rare diseases and looks into the prospects of the application in the rare diseases.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system, with the incidence rate ranging from 0.1% to 12%, and 80% occurring within the first 4 months of ICI application. It can cause lesions in various parts of the nervous system, including aseptic meningitis, meningoencephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis and other central nervous system diseases. It can also cause cranial peripheral neuropathy, multifocal radicular neuropathy, Guillain-Barre syndrome, spinal radicular neuropathy and myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be made by sufficient collection of disease manifestations combined with imaging, cerebrospinal fluid examinations, electro-encephalogram or electro myography to exclude infection or tumor progression. In the treatment of severe cases, ICIs should be discontinued and treated with high doses of glucocorticoid or gamma globulin with systemic support. After neurological adverse reactions, the prognosis of severe cases is poor.

Objective: To summarize the clinical characteristics and nerve conduction damage in patients with early POEMS syndrome, and to explore the value of segment nerve conduction velocity in the diagnosis of POEMS syndrome. Methods: A total of 73 patients with POEMS syndrome and 27 healthy controls in Peking Union Medical College Hospital from September 2009 to June 2019 were recruited in this study. The motor and sensory nerve conduction characteristics of median, ulnar, tibial, and peroneal nerves and the clinical features of the participants were analyzed. The analysis parameters included: (1) distal motor latency (DML), compound muscle action potential (CMAP); (2) the median velocity from elbow to wrist, the median velocity from axillary to elbow, the ulnar velocity from the site below elbow to wrist, the ulnar velocity from the site above elbow to below elbow, the ulnar velocity from axillary to the site above elbow, the tibial velocity from ankle to knee, the peroneal velocity from ankle to fibulae capitulum; (3) sensory nerve conduction velocity and amplitude of these nerves; (4) terminal latency indices (TLI) of median; (5) motor nerve conduction blocks. Results: Peripheral nerve damages were the initial symptoms in thirty-two patients in this group, accounting for 43.8% (32/73), and 81.3% (26/32) of these patients only showed numbness in lower extremities. All POEMS syndrome patients with numbness had abnormal sensory nerve conduction, and 9.5% (7/73) of patients without sensory symptoms also had abnormal sensory nerve conduction. On the other hand, the decrease of CMAP amplitude corresponded to clinical muscle strength decline and motor dysfunction. In the patients with POEMS syndrome, motor nerve conduction in the lower limbs were more likely to be affected and the damages were more severe than in the upper limbs: the proportion of CMAP disappearance in the lower limbs and upper limbs was 47.6% (112/235) vs 2.8% (7/252; χ²=133.698, P<0.01). Sensory nerve conduction damage was more severe than motor nerve conduction: the proportion of amplitude disappearance in sensory and motor conduction was 43.0% (141/328) vs 24.4% (119/487; χ²=133.698, P<0.01). The slowing of motor nerve conduction velocity was more common than the decrease of CMAP amplitude: the rate of slowing down of motor nerve conduction was 88.7% (432/487), and the rate of decrease of amplitude was 52.8% (257/487; χ²=151.905, P<0.01). The DML of median and ulnar nerve in the POEMS syndrome group was longer than that in the control group (median nerve: 4.4 (3.7, 5.0) ms vs 3.2 (3.0, 3.5) ms, U=854.000, P<0.01; ulnar nerve: 3.1 (2.7, 3.8) ms vs 2.5 (2.2, 2.7) ms, U=1 077.500, P<0.01). The TLI of median nerve in patients with POEMS syndrome was significantly higher than that of healthy controls (0.40±0.11 vs 0.35±0.06, t=3.466, P=0.001). There was no statistically significant difference in nerve conduction velocity between the forearm segment and the upper arm segment in the POEMS group. Conclusions Neurological damages were common in patients with POEMS syndrome with sensory nerve damage often being the initial clinical manifestation. In patients with POEMS syndrome, the nerve damage in the lower limbs was more severe than in the upper limbs, and sensory nerve damage was more severe than motor nerve damage. Segmental motor nerve conduction results suggested that demyelination damage occurred earlier than axonal damage, and proximal lesions were slightly heavier than distal lesions. No conduction block was detected in these patients. These characteristics of segmental nerve conduction can provide more evidence for clinical diagnosis of POEMS syndrome.

Objective To investigate the clinical and electrophysiological characteristics of anti-myelin-associated glycoprotein (MAG)-associated peripheral neuropathy, as well as its antibody detection methods, treatment and prognosis. Methods Six cases of IgM paraproteinemia and anti-MAG antibody-associated peripheral neuropathy were summarized. All of the patients came from Peking Union Medical College Hospital and Qilu Hospital since April 2014 to February 2018. The clinical features, electrophysiological characteristics, and auxiliary examinations including anti-MAG antibody results were analyzed, and the treatment and prognosis were followed. Results Of the six patients, five were male and one was female. The age of onset was 50-77 years and the duration was three months to six years. All the six cases suffered from numbness of distal limbs and gradually progressed to the proximal limbs, of which three cases had muscle weakness. Walking instability occurred in five cases. One patient had electricity-like pain in the lower extremities. Reflexes in the four limbs decreased in five cases, and gloves and socks-like deep sensation decreased in six cases. Five patients underwent lumbar puncture and the cerebral spinal fluid protein ranged from 0.75 to 1.33 g/L. Serum monoclonal proteins were found in six patients, of which four were IgM kappa and two were IgG kappa and IgM kappa biclonal. Four cases were diagnosed with monoclonal gammopathy of undetermined significance and two cases were diagnosed with Waldenstr?m's macroglobulinaemia. Abnormal electromyography was detected in all the six cases, suggesting demyelinating peripheral nerve damage with secondary axonal damage, which was sensory predominant and more severe in lower limbs than upper limbs. In all the six cases, anti-MAG-IgM antibodies were all positive by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues. After the diagnosis, three patients underwent RCD (rituxima + dexamethasone + cyclophosphamide) chemotherapy. One patient improved (the modified Rankin scale (mRS) score was 3 before treatment and 2 three years after treatment), one patient was stable, and one patient was still in follow-up. One patient was treated with rituxima, and the condition improved (the mRS score was 3 before treatment and 1 one year after treatment). Conclusions MAG-associated peripheral neuropathy can present a slow progressed distal symmetric sensomotor peripheral neuropathy with predominant sensory symptoms. Electromyography shows demyelinating change. Monoclonal protein is usually IgM kappa. MAG-IgM antibodies detection by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues can support the diagnosis. RCD chemotherapy may be effective.

Objective To investigate the characteristics of giant F-waves in patients with amyotrophic lateral sclerosis ( ALS ) and the relationship between giant F-waves and disease phenotype . Methods Motor nerve conduction study and F-waves were performed to the median , ulnar, tibial and peroneal nerves of 55 patients with ALS and 52 healthy volunteers.A series of 100 electrical stimuli were employed to obtain F-waves.The following F-wave variables were estimated: frequency of giant F-waves, frequency of patients with giant F-waves, the relationship between giant F-waves and lower motor neuron dysfunction , the relationship between giant F-waves and upper motor neuron dysfunction , the relationship between giant F-waves and disease duration , the relationship between giant F-waves and disease severity , and the relationship between giant F-waves and disease progression rate ( DPR).Results The frequencies of giant F-waves ( ALS: median nerve 0.00 ( 0.00 )%, ulnar nerve 0.00 ( 1.02 )%, tibial nerve 0.00 (0.00)%,peroneal nerve 0.00(0.00)%.Normal controls:median nerve 0.00(0.00)%,Z=-2.360, P=0.018;ulnar nerve 0.00(0.00)%,Z=-3.997,P<0.01;tibial nerve 0.00(0.00)%,Z=-3.006, P=0.003;peroneal nerve 0.00(0.00)%,Z=-3.006,P=0.003) and the frequencies of patients with giant F-waves (ALS:median nerve 13/55,23.6%,ulnar nerve 26/55,47.2%,tibial nerve 18/55,32.7%, peroneal nerve 16/55, 29.1%.Normal controls:median nerve 4/52,7.7%,χ2 =0.024,P=0.024;ulnar nerve 7/52,13.5%, χ2 =14.326,P<0.01; tibial nerve 6/52,11.5%, χ2 =6.897,P=0.009; peroneal nerve 6/52,11.5%,χ2 =5.042,P=0.025) in the median nerve, ulnar nerve, tibial nerve and peroneal nerve were significantly increased compared with those of the normal controls .No significant differences were found in the frequencies of upper motor neuron dysfunction between nerves with giant F -waves and nerves without giant F-waves in the median nerves , ulnar nerves , tibial nerves and peroneal nerves of ALS patients . The compound muscle action potential amplitude of nerves with giant F-waves was significantly higher than those of nerves without giant F-waves in the median nerves (11.20(5.80) mV vs 5.90(8.50) mV,t=2.883,P=0.004)and tibial nerves ((13.20 ±4.61) mV vs (10.69 ±4.76) mV,t=-2.222,P=0.028) of the ALS patients.No significant correlation was detected between the frequency of giant F-waves and disease duration or ALS functional rating scale in the ALS patients , while the frequency of giant F-waves correlated inversely with the DPR(r=-0.287,P=0.034).No significant differences were detected in disease duration between ALS patients with giant F-waves and those without giant F-waves.Compared with those in ALS patients without giant F-waves, the revised ALS Functional Rating Scale score (37.00(3.00) vs 42.00(4.75),Z=3.197,P=0.001) was more, the DPR (0.50(0.35)vs 0.90(0.43),Z=-3.033, P=0.002 ) was slower in ALS patients with giant F-waves. Conclusions The giant F-waves were significantly increased in the ALS patients than those in the healthy volunteers and were distributed asymmetrically between the left and right sides .These electrophysiological characteristics of ALS patients fitted well with progressive loss of anterior horn cells , and indicated differential involvement of different spinal motoneuron pools in the ALS patients .No correlations were found between the frequency of giant F-waves and disease duration .The appearance of giant F-waves may indicate loss of spinal motoneuron early in the disease course , and may suggest that the degree of reinnervation and functional compensation are relatively good after motoneuron loss .