Diagnosis and treatment of POEMS syndrome / 中华神经科杂志

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.

Complement Inhibitors in Rare Diseases / 罕见病研究

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.

Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer / 中国肺癌杂志

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.

Motor nerve conduction and clinical characteristics of POEMS syndrome / 中华神经科杂志

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.

Clinical Diagnosis and Treatment Recommendations for Adverse Reaction in the Nervous System Related to Immunocheckpoint Inhibitor / 中国肺癌杂志

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.

Myelin-associated glycoprotein associated neuropathies: clinical features and antibody detection / 中华神经科杂志

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.

Low frequency repetitive nerve stimulation in anti-muscle specific tyrosine kinase receptor antibody positive myasthenia gravis / 中华神经科杂志

Objective To describe the repetitive nerve stimulation ( RNS) in anti-muscle specific tyrosine kinase (anti-MuSK) receptor antibody positive myasthenia gravis (MG), and compare with anti-acetylcholine receptor ( AChR ) positive myasthenia gravis , to figure out characteristics of anti-MuSK receptor MG.Methods We analyzed clinical and RNS data of nine anti-MuSK receptor MG and 19 age-and sex-matched anti-AChR MG.RNS was performed to the abductor digiti minimi , orbicularis oculi or musculus frontalis and trapezius .Results In anti-MuSK receptor MG , abnormal RNS in facial nerve was seen in 6/9 and in trapezius was 5/9, in limbs was 0.In anti-AChR MG, abnormal RNS in facial nerve was seen in 13/19, in trapezius was 18/19 and in limbs was 7/19.Abnormal in any of three parts was 8/9 and 19/19 in anti-MuSK receptor MG and anti-AChR MG, respectively.The RNS decrementing was more obvious in facial nerve in anti-Musk receptor MG than in anti-AChR MG.Negative prostigmin test was independently associated with anti-MuSK receptor MG (OR=4.25,95% CI 2.19 -15.25, P=0.015). Conclusions Abnormal RNS in any of three parts is more pronounced in anti-AChR MG compared with anti-MuSK receptor MG.RNS decrementing in facial nerve is more obvious in anti-AChR MG.Negative prostigmin test can aid in early suspicion in anti-MuSK receptor MG.

Characteristics of giant F-waves in amyotrophic lateral sclerosis / 中华神经科杂志

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 .

Low frequency repetitive nerve stimulation in anti-muscle specific tyrosine kinase receptor antibody positive myasthenia gravis / 中华神经科杂志

Objective To describe the repetitive nerve stimulation ( RNS) in anti-muscle specific tyrosine kinase (anti-MuSK) receptor antibody positive myasthenia gravis (MG), and compare with anti-acetylcholine receptor ( AChR ) positive myasthenia gravis , to figure out characteristics of anti-MuSK receptor MG.Methods We analyzed clinical and RNS data of nine anti-MuSK receptor MG and 19 age-and sex-matched anti-AChR MG.RNS was performed to the abductor digiti minimi , orbicularis oculi or musculus frontalis and trapezius .Results In anti-MuSK receptor MG , abnormal RNS in facial nerve was seen in 6/9 and in trapezius was 5/9, in limbs was 0.In anti-AChR MG, abnormal RNS in facial nerve was seen in 13/19, in trapezius was 18/19 and in limbs was 7/19.Abnormal in any of three parts was 8/9 and 19/19 in anti-MuSK receptor MG and anti-AChR MG, respectively.The RNS decrementing was more obvious in facial nerve in anti-Musk receptor MG than in anti-AChR MG.Negative prostigmin test was independently associated with anti-MuSK receptor MG (OR=4.25,95% CI 2.19 -15.25, P=0.015). Conclusions Abnormal RNS in any of three parts is more pronounced in anti-AChR MG compared with anti-MuSK receptor MG.RNS decrementing in facial nerve is more obvious in anti-AChR MG.Negative prostigmin test can aid in early suspicion in anti-MuSK receptor MG.

Characteristics of giant F-waves in amyotrophic lateral sclerosis / 中华神经科杂志

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 .

The characteristics of F-waves in patients with Kennedy's disease / 中华神经科杂志

Objective To investigate the characteristics of F-waves in patients with Kennedy's disease.Methods Thirty two patients with Kennedy's disease and 30 male healthy volunteers,who visited the Department of Neurology,Peking Union Medical College Hospital between August 2013 and July 2014,were recruited consecutively for this study.Motor nerve conduction study and F-wave examination were performed on the median,ulnar,tibial and peroneal nerves of all participants.A series of 100 electrical stimuli were employed to obtain F-waves.The F-wave parameters in all tested nerves were compared between patients with Kennedy's disease and normal controls including F-wave minimum latency,F-wave persistence,mean and maximum F-wave amplitude,the frequency of giant F-waves.Results The mean Fwave amplitude (median nerve:patients with Kennedy's disease 375.0 (298.3) μV,healthy volunteers 297.0(145.0) μV,Z =-3.378,P ＜0.01;ulnar nerve:patients with Kennedy's disease 397.5(295.0) μV,healthy volunteers 293.0 (101.8) μV,Z =-3.968,P ＜ 0.01;tibial nerve:patients with Kennedy's disease 374.5 (227.3) μV,healthy volunteers 294.0 (160.5) μV,Z =-3.144,P =0.002;peroneal nerve:patients with Kennedy's disease 346.5 (292.8) μV,healthy volunteers 146.5 (69.3) μV,Z =-6.864,P ＜ 0.01),maximum F-wave amplitudes (median nerve:patients with Kennedy's disease 1 291.0 (952.0) μV,healthy volunteers 846.5 (523.0) μV,Z =-4.823,P ＜ 0.01;ulnar nerve:patients with Kennedy's disease 1 663.5 (1 374.0) μV,healthy volunteers 760.5 (341.8) μV,Z =-6.813,P ＜ 0.01;tibial nerve:patients with Kennedy's disease (1 054.1 ± 451.6) μV,healthy volunteers (652.5-± 172.5) μV,t =5.380,P ＜ 0.01;peroneal nerve:patients with Kennedy's disease (840.4 ± 494.1) μV,healthy volunteers (370.2 ± 202.0) μV,t =6.475,P ＜ 0.01),frequency of giant F-waves (median nerve:patients with Kennedy's disease 0.0％ (7.2％),healthy volunteers 0.0％ (0.0％),Z =-5.149,P ＜ 0.01;ulnar nerve:patients with Kennedy's disease 3.1％ (10.5％),healthy volunteers 0.0％ (0.0％),Z =-7.026,P ＜0.01;tibial nerve:patients with Kennedy's disease 0.0％ (3.3％),healthy volunteers 0.0％ (0.0％),Z =-4.651,P ＜0.01;peroneal nerve:patients with Kennedy's disease 3.3％ (28.2％),healthy volunteers 0.0％ (0.0％),Z =-5.532,P ＜0.01),and frequencies of patients with giant F-waves (median nerve:patients with Kennedy's disease 78.1％ (25/32),healthy volunteers 10.0％ (3/30),x2 =29.016,P ＜ 0.01;ulnar nerve:patients with Kennedy's disease 87.5％ (28/32),healthy volunteers 10.0％ (3/30),x2 =37.200,P ＜ 0.01;tibial nerve:patients with Kennedy's disease 62.5％ (20/32),healthy volunteers 6.7％ (2/30),x2 =21.085,P ＜ 0.01;peroneal nerve:patients with Kennedy's disease 68.8 ％ (22/32),healthy volunteers 10.0％ (3/30),x2 =22.209,P ＜ 0.01) in all nerves examined were significantly higher in patients with Kennedy's disease than in the normal controls.The F-wave persistence in all nerves examined was significantly lower than in the normal controls (median nerve:patients with Kennedy's disease 52.5％ (36.3％),healthy volunteers 98.0％ (7.0％),Z =9.010,P ＜ 0.01;ulnar nerve:patients with Kennedy's disease 71.0％ (28.3％),healthy volunteers 100.0％ (1.0％),Z =9.455,P ＜ 0.01;tibial nerve:patients with Kennedy's disease 100.0％ (2.0％),healthy volunteers 100.0％ (0.0％),Z =4.255,P ＜ 0.01;peroneal nerve:patients with Kennedy's disease 33.1％ ± 23.9％,healthy volunteers 46.9％ ± 27.2％,t =-2.848,P =0.007).Giant F-waves were detected in multiple nerves and often appeared symmetrically on the same nerves between the left and right sides in patients with Kennedy's disease.No significant correlations were found between the pooled frequency of giant F-waves and disease duration in patients with Kennedy's disease(r =0.162,P =0.418).Conclusions The results showed increased F-wave amplitudes,increased number of giant F-waves,especially giant F-waves detected in multiple nerves or appearing symmetrically combined with low persistence,consistent with the pathologic features of chronic and unselected loss of anterior horn cells in patients with Kennedy's disease.

Split-hand sign in the patients with amyotrophic lateral sclerosis / 中华神经科杂志

Objective To investigate the diagnostic value of the split-hand sign in amyotrophic lateral sclerosis ( ALS).Methods Ninety ALS patients, 41 patients with other neuromuscular disorders and 71 normal controls were recruited for conventional nerve conduction study.Compound muscle action potential ( CMAP) amplitude recorded from abductor pollicis brevis ( APB) , abductor digiti minimi ( ADM) and first dorsal interosseous (FDI), CMAP amplitude ratios, CMAP amplitude differences and split-hand index ( SI) were analyzed.Results The APB/ADM CMAP amplitude ratio was significantly lower in the ALS patients (0.44(0.44)) than that in the patients with other neuromuscular disorders (1.31(0.87);z=6.967, P<0.01) and the normal controls (0.99(0.42);z=7.687, P<0.01).The FDI/ADM CMAP amplitude ratio was significantly decreased in the ALS patients ( 0.79 ( 0.46 ) ) compared with that in the normal controls ( 1.23 ( 0.39 ); z =5.899, P <0.01 ).The FDI/ADM CMAP amplitude ratio was comparable between the ALS patients and the patients with other neuromuscular disorders ( 0.93 ( 0.62 );z=1.737,P=0.081).SI was significantly lower in the ALS patients (2.42 (3.14)) than that in the patients with other neuromuscular disorders (10.10(6.54);q=7.947, P<0.05) and the normal controls (17.93(8.32);q=10.827, P<0.05).SI <5.2 can help differentiate ALS from mimic disorders, with a sensitivity of 83.33% and specificity of 96.43%.Conclusions The split-hand sign appears to be a specific feature of ALS.SI robustly differentiates ALS from mimic disorders and potentially facilitates an earlier diagnosis of ALS.

The utility of peripheral nerve ultrasound in differentiating Charcot-Marie-Tooth type 1 from chronic inflammatory demyelinating polyradiculoneuropathy / 中华神经科杂志

Objective To determine whether peripheral nerve ultrasound can differentiate CharcotMarie-Tooth type 1 (CMT1) from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Methods Eighteen patients with CIDP,13 patients with CMT1 and 16 healthy controls were recruited prospectively from Peking Union Medical College Hospital between January 2014 and July 2015 for this study.Ultrasonographic tests were performed via nerve tracing from wrist to axilla on median and ulnar nerve with a 10 MHz linear array probe.The cross sectional areas (CSAs) were measured at 10 defined sites of the nerves,respectively.Results CSAs (mm2) at all sites of median nerve were significantly increased in CMT1 than in CIDP (10.5 ±5.3 vs7.8 ±2.4,10.9 ±3.6 vs 6.8 ±1.9,11.5 ±5.0 vs7.3 ±1.8,13.5 ± 4.4vs7.2±2.5,16.0±4.5vs7.2±2.1,17.1±5.1vs7.0±2.8,21.0±4.5vs9.5±4.8,24.3±6.9 vs 9.5 ±4.3,23.9 ±6.0 vs 10.2 ±4.3,22.4 ±6.7 vs 9.8 ±2.1;t=2.141,4.766,2.935,4.858,6.715,6.602,7.148,7.100,8.078,6.498,respectively,all P ＜ 0.05).CSAs (mm2) at all sites of ulnar nerve were significantly increased in CMT1 than in CIDP (7.9 ± 1.8 vs 4.0 ± 1.3,8.9 ± 2.0 vs 4.9 ± 1.3,13.5±1.9 vs6.5±2.4,15.0±4.3 vs 6.5 ±1.5,15.8 ±4.4 vs 6.8 ±3.3,11.6±2.3 vs6.9± 3.1,10.2±3.2vs7.6±2.8,14.0±3.0vs6.6±2.1,19.2±3.7vs7.6±4.4,18.1±3.6vs6.3± 2.5;t =7.652,7.414,9.194,6.893,6.443,4.766,2.561,7.897,8.113,11.554,respectively,all P ＜ 0.05).CSAs at 8 sites of median nerve and 8 sites of ulnar nerve were significantly increased in CIDP than in healthy controls.Receiver operation characteristic curve analysis revealed that CSA was suited for differentiating CMT1 from CIDP,and the area under curve in 8 sites of median nerve and 9 sites in ulnar nerve was more than 0.9.Conclusions CSAs measured at different sites by peripheral nerve ultrasound in CMT1 were significantly increased than in CIDP.Measurement of CSAs by peripheral nerve ultrasound can be used for differentiating CMTI from CIDP.

Relationship between cervical spondylotic radiculopathy and carpal tunnel syndrome / 中华神经科杂志

Objective To explore the relationship between cervical spondylotic radiculopathy (CSR) and carpal tunnel syndrome (CTS) by investigating their electrophysiological characteristics and the incidence of CSR root injury and root injury complicating with CTS.Methods One hundred and twenty-four cases of CSR diagnosed in Peking Union Medical College Hospital from September 2013 to February 2014 by electromyography (EMG) were recruited.According to the results of EMG,patients were divided into root injury and root injury complicating with CTS groups.The distal motor latency (DML),motor nerve conduction velocity (MCV),sensory nerve conduction velocity (SCV),sensory nerve action potential (SNAP),compound muscle action potential (CMAP) and spontaneous potential (SP) were compared between the two groups.Results There were 81 (65.3％) cases with root injury,11 cases with double sides injury and 29 cases with normal EMG among these 124 patients.The CMAP,DML,MCV,SCV and SNAP were normal in 76 cases,CMAP lowered 5％-12％ in 3 cases,DML extended 3％ and 9％ in 2 cases.There were 14 cases (11.3％) with concomitant CTS (female 10 cases and male 4 cases,double sides CTS 10 cases).Among the 14 cases with concomitant CTS,there were 9 cases with simply sensory nerve conduction abnormality,SCV slowing down 26％-47％,SNAP reducing 58％-86％ or normal,while other 5 cases with motor conduction abnormality as well as sensory nerve conduction abnormality,CMAP reducing 21％-78％,DML extending 27％-39％ in 3 cases,MCV slowing down 32％ and 40％ in 2 cases.Five cases had spontaneous electricity position movement in the abductor pollicis brevis.The incidence of root injury complicating with CTS in C6 (27.4％,9/33),C7 (26.9％,7/26) and C8 (5/7) showed statistically significant difference (x2 =5.96,P ＜ 0.01).Conclusions There is a high incidence of root injury and CTS in CSR patients,indicating a possible double crush between CSR and CTS.

Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis / 中华神经科杂志

Objective To evaluate the diagnostic accuracy of diffusion tensor imaging (DTI) of corticospinal tract in amyotrophic lateral sclerosis (ALS) and find optimal testing strategies and optimal cutoff values of DTI indices for individual patient discrimination.Methods Thirty-three ALS patients and 34 healthy controls,collected at Peking Union Medical College Hospital from June 2004 through July 2005,undergoing brain DTI studies and fractional anisotropy (FA) examinations along the corticospinal tract,were analyzed by receiver operating characteristic (ROC) curves.Results Compared with the controls,ALS group had significantly decreased FA values in subcortical white matter of the precentral gyrus,the posterior limb of the internal capsule and the cerebral peduncle.In ROC analysis,the average FA value of the former two positions showed the best performance with an area under the curve of 0.917,an optimal cut-off value of 0.604,a sensitivity of 0.759 and a specificity of 0.912.The corresponding data for the average FA of all the three positions and each single position were listed as follows:average of three 0.914,0.648,0.759,0.912; precentral gyrus 0.875,0.509,0.733,0.824; internal capsule 0.845,0.692,0.656,0.941 ; and cerebral peduncle 0.752,0.742,0.656,0.735.Conclusions FA values of the corticospinal tract have a good accuracy in detecting upper motor neuron involvement in ALS.Precentral gyrus and posterior limb of the internal capsule and the average FA values of these two positions were suggested as the preferred testing places and DTI indices for clinical use.

The relationship between muscle strength, creatine kinase and electromyography in lipid storage myopathy / 中华神经科杂志

Objective To assess the relationship between muscle strength , creatine kinase ( CK) and electromyography ( EMG) in patients with lipid storage myopathy ( LSM).Methods Motor and sensory nerve conduction study, F wave, and quantity EMG were performed in 30 patients with LSM.Muscle strength and CK were studied before EMG.The relationship between EMG , muscle strength and CK were analyzed.Results EMG showed myopathic changes in 19 patients,myopathic coexistence with neuropathic changes in five , and neuropathic changes in two.Four patients had normal EMG.Motor nerve conduction studies showed decreased compound muscle action potential amplitude in seven nerves of two patients , while abnormal sensory nerve conduction in 16 nerves of five patients.Quantity EMG was performed in 78 muscles.Thirty-eight muscles of 21 patients had decreased amplitude and short duration motor unit potential ( MUP) , 6 muscles of 2 patients had increased amplitude and long duration MUP , and 30 muscles of 16 patients had normal MUP.Abnormal spontaneous activities ( SA) were detected in 16 muscles.The M( Q25 , Q75 ) of serum CK was 295.5 (201.0, 4 845.8) U/L in patients with abnormal SA in EMG , and 482.0 (292.8, 963.8) U/L in patients without abnormal SA in EMG (Z=0.281, P=0.778).Medical Research Council ( MRC) Scale in deltoid muscle was 4.3 ±0.7 in muscles with SA and 4.1 ±0.8 in muscles without SA (t=0.490, P=0.628), and that in quadriceps femoris was 3.9 ±0.6 for muscles with SA and 3.7 ± 0.6 for muscles without SA ( t =0.725 , P =0.474 ).MRC Scale in deltoid muscle was 4.1 ±0.7 in muscles with myogenic MUP and 4.1 ±0.9 in muscles without myogenic MUP ( t=0.101, P=0.920), which in quadriceps femoris was 3.8 ±0.6 for muscles with myogenic MUP and 3.7 ±0.7 for muscles without myogenic MUP ( t=0.368 , P=0.716 ).Conclusions Neurogenic or normal MUP and abnormal sensory nerve conduction can be presented in some patients with LSM , while SA is not common.The changes in MUP and SA are neither correlated with CK nor with muscle strength.

Evaluation of neostigmine test in diagnosis of myasthenia gravis initiated from extrocular muscles / 中华神经科杂志

Objective To investigate the usage of neostigmine test in diagnosis of myasthenia gravis (MG) initiated from extraocular muscles,including test methods and data analysis.Methods The clinical features of 100 consecutive patients with myasthenia gravis initiated from extraocular muscles were collected retrospectivelly,including initial symptom,number and department of visiting,evolution of symptoms and signs,methods and the judgment of therapeutic response for neostigmine test.Results (1) All patients with MG started from ptosis unilateral or bilateral or diplopia,among which 46％ (46/100)of patients with both ptosis and diplopia.Within 21％ (21/100) of patients,other muscles had been involved except for extrocular muscles before neostigmine test.Seventy-eight percent patients first consulted ophthalmology after (0.7 ± 0.3) month from onset.It took (1.6 ± 1.3) months for patients to visit neurologist for the first time.The average time for confirming diagnosis was (3.3 ± 2.1) months.(2) After (2.0 ± 1.5) times consulted at neurology department and (2.0 ± 1.8) months after symptoms onset,the patients undergone neostigmine test.Positive reaction rate showed lower in low dosage group (60.9％ (14/23) vs 98.3％ (58/59),x2 =18.30,P ＜0.01).Positive rate also showed lower in oral-take pyridostigmine bromide tablets group than neostigmine methylsulfate injection group(15/18 vs 98.3％ (58/59),x2 =4.428,P =0.035).(3) Sixtyfive percent patients had mild to moderate side effects after neostigmine injection,which disappeared in 60-120 minutes.Conclusions Non-standard operations of neostigmine test reduced the effectiveness of its diagnosis for MG initiated from extraocular muscles.Neurologist should attach importance totake standard neostigmine test to identify MG as soon as possible.

Progression from ocular to generalized myasthenia gravis in adults / 中华神经科杂志

Objective To investigate the time and rate of generalization developed from ocular symptoms in adults to generalized myasthenia gravis (GMG).Methods The data from 456 adult patients who started on ocular symptoms during Jan 2005 to Jan 2012 were retrospectively studied,with a follow-up period of 3 months to 17 years.The data included transfer time,Osserman type,difference between steroids group and no-steroids group.Results (1) During the follow-up period,197 (43.2％) patients developed to generalized myasthenia gravis,58.4％ (115/197)in one year after onset of ocular symptoms,74.1％ (146/197) in 2 years and 80.7％ (159/197) in 3 years.86.8％ (171/197) developed to Osserman Ⅱ a or Ⅱ b.(2) Of 233 patients untreated with steroids,134 (57.5％) developed to GMG,while 63 (28.3％) of 223 patients who were treated with steroids developed to GMG (x2 =38.57,P ＜ 0.01).There were no difference between two groups in transfer time and Osserman type.Conclusion MG initiated from ocular syndromes in adults easily develops to GMG in 2 years.Patients treated with steroids have low chance of generalization.

Diffuse neurogenic changes on electromyography and diagnosis of amyotrophic lateral sclerosis / 中华神经科杂志

Objective To explore the correlation between diffuse neurogenic changes on electromyography and diagnosis of amyotrophic lateral sclerosis (ALS).Methods Retrospective study was performed based on database of motor neuron disorders collected from January,2002 to December,2008.The category of disease with diffuse neurogenic changes at the first examination was summarized.The electromyography (EMG) manifestation in ALS patients at the first examination and the results after follow-up were reviewed.The factors affecting EMG manifestation in ALS were analyzed with binary Logistic regression.Results In 298 patients with diffuse neurogenic changes on EMG,192 cases (64.4％ ) were diagnosed of ALS,36 ( 12.1％ ) progressive muscular atrophy,13 (4.4％ ) Kennedy' s disease,10 (3.4％)Hirayama disease,9 ( 3.0％ ) cervical spondylosis combined with lumbar spondylosis,6 ( 1.3％ ) spinal muscular disease,5 ( 1.7％ ) multifocal motor neuropathy,5 ( 1.7％ ) ALS-plus disease,4 ( 1.3％ )myopathy,3( 1.0％ ) hereditary motor neuropathy,3 ( 1.0％ ) axonal motor neuropathy,2(0.7％ ) postpolio syndrome,and 10 (3.4％) with no definite diagnosis.In total 213 patients who were diagnosed with ALS after follow-up,at their first examinations,8 (3.8％) had neurogenic changes in two regions and 13(6.1％ ) had neurogenic changes in one region,and they all developed to diffuse neurogenic changes after follow-up for 3 to 24 months.Logistic regression analysis showed that the EMG change at first examination was not related to duration from onset,symptom location at onset,age at onset and gender.Conclusion Diffuse neurogenic changes on EMG can present in many disease including ALS.Neurogenie changes in one or two regions on EMG can be the manifestation of ALS at early stage.

Clinical and electrophysiological study of Miller-Fisher syndrome and Bickerstaff' s brainstem encephalitis / 中华神经科杂志

Objective To investigate the underlying mechanisms of Miller-Fisher syndrome (MFS) and Bickerstaff' s brainstem encephalitis (BBE) by studying their clinical and electrophysiological characteristics.Methods The clinical and electrophysiological characteristics of 13 MFS and 7 BBE cases in Peking Union Medical College Hospital between 2000 and 2011 were retrospectively analyzed.The electrophysiological parameters included sensory and motor nerve conduction,electromyography,F wave,sympathetic skin response and brainstem auditory evoked potential and blink reflex.Results MFS and BBE had similar clinical characteristics:respiratory symptoms were the most common infectious symptoms before disease onset; Ophthalmoplegia,facial palsy and bulbar symptoms were common; They both had cerebrospinal fluid albuminocytological dissociation and positive serum anti-GQ1b antibody.However,BBE had more central nervous system lesion signs clinically such as conscious disturbance,positive Babinski' s sign and central facial palsy.Electrophysiologically,MFS and BBE also had similar electrophysiological features:sensory nerve abnormality ratios were 6/13,2/7 respectively,with prominently reduced sensory nerve active potential amplitude,normal or slightly slowed sensory conduction velocity; Motor nerves abnormality ratios were 2/13,1/7 respectively,with slightly prolonged distal motor latency and normal compound muscle action potential; Electromyography abnormality ratios were 1/7,0/4 respectively; F wave frequency abnormality ratios were 3/13,5/7 respectively,and in some cases,F wave frequency would restore; Sympathetic skin response abnormality ratios were 1/2,1/3 respectively; Blink reflex abnormalityratios were 1/2,1/1 respectively,with central involvement in BBE; Brainstem auditory evoked potential abnormality ratios were 3/5,1/4 respectively,with wave Ⅰ latency or amplitude abnormality.Conclusion The similarities of clinical and electrophysiological features suggest that MFS and BBE have the same mechanism and they form a continuous spectrum with variable central nervous system and peripheral nervous system involvement.