Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Pathologic features of paraspinal muscle biopsies in patients with adolescent idiopathic scoliosis / 北京大学学报(医学版)

OBJECTIVE@#To characterize the paraspinal muscles of adolescent idiopathic scoliosis (AIS) patients, and to further explore its etiology.@*METHODS@#Clinical records and paraspinal muscle biopsies at the apex vertebra region during posterior scoliosis correction surgery of 18 AIS were collected from November 2018 to August 2019. Following standardized processing of fresh muscle tissue biopsy, serial sections with conventional hematoxylin-eosin (HE) and histochemical and immunohistochemical (IHC) with antibody Dystrophin-1 (R-domain), Dystrophin-2 (C-terminal), Dystrophin-3 (N-terminal), Dystrophin-total, Myosin (fast), major histocompatibility complex 1 (MHC-1), CD4, CD8, CD20, and CD68 staining were obtained. Biopsy samples were grouped according to the subjects' median Cobb angle (Cobb angle ≥ 55° as severe AIS group and Cobb angle < 55° as mild AIS group) and Nash-Moe's classification respectively, and the corresponding pathological changes were compared between the groups statistically.@*RESULTS@#Among the 18 AIS patients, 8 were in the severe AIS group (Cobb angle ≥55°) and 10 in the mild AIS group (Cobb angle < 55°). Both severe and mild AIS groups presented various of atrophy and degeneration of paraspinal muscles, varying degrees and staining patterns of immune-expression of Dystrophin-3 loss, especially Dystrophin-2 loss in severe AIS group with significant differences, as well as among the Nash-Moe classification subgroups. Besides, infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons was observed in all the patients while CD20+ cells were null. The expression of MHC-1 on myolemma was present in some muscle fibers.@*CONCLUSION@#The histologic of paraspinal muscle biopsy in AIS had similar characteristic changes, the expression of Dystrophin protein was significantly reduced and correlated with the severity of scoliosis, suggesting that Dystrophin protein dysfunctions might contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS were mainly manifested by T cell infiltration, and there seemed to be a certain correlation between inflammatory cell infiltration, MHC-1 expression and abnormal expression of Dystrophin. Further research along the lines of this result may open up new ideas for the diagnosis of scoliosis and the treatment of paraspinal myopathy.

Diagnostic value of F wave changes in patients with Charcot-Marie-Tooth1A and chronic inflammatory demyelinating polyneuropathy / 北京大学学报(医学版)

OBJECTIVE@#To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP).@*METHODS@#Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared.@*RESULTS@#The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ2=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody.@*CONCLUSION@#The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.

Diagnostic value of tremor analysis in identifying the early Parkinson's syndrome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the diagnostic value of tremor analysis in early stages of Parkinson's syndrome, when the clinical symptoms of tremor onset are not unilaterally often able for a definite diagnosis to be made.@*METHODS@#We included 70 patients with unilateral tremor, under 45 years old and disease duration within 3 years enrolled in Peking University Third Hospital from January, 2014 to December 2015. We recorded clinical features, unified Parkinson's disease rating scale (UPDRS)-III, non-motor symptom (NMS) scores. Tremor analysis and transcranial sonography were performed for all the patients. Based on the results of tremor analysis, we arbitrarily divided the patients into 3 groups: (1) The patients with classical Parkinson's syndrome manifestations on one side (25 cases); (2) The patients with classical Parkinson's syndrome manifestations on both sides (15 cases); (3) The patients with no classical Parkinson's syndrome manifestations (30 cases). The patients were monitored every 6 months to 3 years, until the final diagnosis was made.@*RESULTS@#There was no significant difference in age, gender distribution, Hamilton depression scale (HAMD) scores and H-Y scores among the three groups (P>0.05). The average UPDRS-III motor scores of the three groups were significantly different (P=0.001), with 18.23, 18.79 and 14.67, respectively. The average scores of NMS were significantly different, with 15.81, 17.07 and 9.90, respectively (P<0.001). The positive rates of transcranial sonography (TCS) in the three groups were 48.0%, 60.0% and 26.67%, with no significant difference (P=0.702). After three years of follow-up, 35 patients (50%) met the diagnostic criteria of Parkinson's disease of International Parkinson and Movement Disorder Society (MDS) in 2015, 19 patients (27.1%) met the criteria of idiopathic tremor, and 7 patients (10%) met the criteria of Parkinson's plus syndrome. The sensitivity and specificity of tremor analysis for early diagnosis of Parkinson's disease were 82.8% and 68.6%, respectively. Compared with TCS, the sensitivity and specificity of TCS were 65.7% and 62.9%. There were consistency (Kappa=0.568) and significant difference (P=0.031) between the two methods.@*CONCLUSION@#Tremor analysis is sensitive and a superior way in identifying early Parkinson's syndrome patients with tremor dominant manifestation. The combination of non-motor symptoms and transcranial sonography are also needed at diagnosis.

The risk factors of primary intracerebral hemorrhage: A comparison between young adults and aged over 45 / 中国脑血管病杂志

Objective: To compare the risk factors of intracerebral hemorrhage (ICH) in young adults and aged over 45. Methods: A total of 274 patients who suffered from the first attack of ICH were collected. Among them 34 were attributed to young adults group, and 240 were aged over 45 group. The incidence of various risk factors were calculated, the differences of risk factors, and the influence of the exposure of various risk factors between these two groups were compared. Results: Hypertension was the most prominent risk factor in patients with ICH in this study, and its incidence was 70.1%, the incidence in the young adult group and the aged over 45 group were 55.9% and 72.0% respectively, but there was no significant difference. Then the subsequent orders were hyperhomocysteinemia, history of ischemic stroke, cigarette smoking and alcoholic consumption. The incidence of history of ischemic stroke in the young adult group was 11.8%, and the aged over 45 group was 31.3%, and there was significant difference between these two groups (P > 0.05). There were no significant differences on hyperhomocysteinemia cigarette smoking and alcoholic consumption in both groups. The patients with the suspected inducing factors before the symptom onset in the young adult group and the aged over 45 group were 50.0% and 24.6% (P < 0.01) respectively. The patients with the inducing factors of fatigue or emotional agitation in both groups were 41.2% and 13.8% (P < 0.01) respectively. The symptom onset of the patients during the active state in both groups were 76.5% and 52.9% (P < 0.05) respectively. The risk factors that closely correlated with the onset of ICH were fatigue and emotional agitation before the hemorrhage in the young adult group (OR 4.370, 95% CI 2.012-9. 490, P < 0.01). Conclusion: History of hypertension is the common risk factors of ICH in the young adults and the aged over 45. Patients with history of ischemic stroke in the aged over 45 group is higher than that in the young adult group. Fatigue or emotional agitation before the symptom onset in the young adult group is higher than the aged over 45 group.

Single neucleotide polymorphisms of the vascular endothelial growth factor gene in Chinese Han population / 中国康复理论与实践

@#ObjectiveTo determine the distribution of the single neucleutide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene in Chinese Han population. Methods252 healthy Chinese Han subjects were studied with PCR technique. The results were compared with the data on European Caucasians reported. ResultsThe frequencies of VEGF gene allele C and A were respectively 71.8% and 28.2%. The genotypes of CC, CA and AA were 48.8%, 46.0% and 5.2%, respectively. The frequencies of VEGF promoter 2578A/A polymorphism in Chinese Han population were significantly different from those in European Caucasian population(P<0.01). Conclusion2578A/A homozygote which results to low VEGF expression of Chinese Han subjects is remarkably less than that of European Caucasians.