Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

Evaluation of chemical similarity among rhizome, pseudo stem and leaf of Musa basjoo by UPLC-ELSD fingerprint combined with chemo metrics methods.

Rhizoma Musa (the Rhizome of Musa basjoo Sied.et Zucc.) is used as a traditional medical herb of Miao nationality in Guizhou province, in China. It has the efficacy of clearing heat and detoxifying, quenching thirst, diuresis, etc. Modern pharmacological studies have shown that it has hypoglycemic, inhibition of α-glucosidase, and anti-inflammatory activity. However, when the rhizomes of Musa basjoo are dug up, the rhizomes are unable regenerate, and the pseudostem and leaf are discarded, which not only pollutes the environment, but also causes a huge waste of herb resources. In this study, a UPLC-ELSD fingerprint analysis with chemometric method was applied for the evaluation of chemical similarity among rhizome, pseudostem and leaf of Musa Basjoo. The results indicated that the combined method could efficiently analyze and compare the chemical similarity among rhizome, pseudostem, and leaf of Musa Basjoo. The proposed method provides the foundation for the resource substitution of the rhizome, pseudostem, and leaf of Musa Basjoo.

Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma.

Glaucoma represents a major cause of blindness, generally associated with elevated intraocular pressure (EIOP). The aim of the present study was to investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs) and the underlying mechanism based on a mouse model of chronic glaucoma with EIOP. The successfully modeled mice were administered with mimics or inhibitors of miR-149. Next, the number of RGCs, ultrastructural changes of RGCs, and purity of RGCs in the retinal tissues were detected. Moreover, the RGCs were collected and subsequently treated with 60 mmHg pressure and transfected with a series of plasmids aiding in the regulation of the expression of miR-149 and betacellulin (BTC). The levels of miR-149, BTC, phosphatidylinositol 3-kinase (PI3K), and Akt were subsequently determined. Finally, RGC viability and apoptosis were detected accordingly. Dual luciferase reporter gene assay provided validation, highlighting BTC was indeed a target gene of miR-149. The downregulation of miR-149 is accompanied by an increased number of RGCs and decreased ultrastructural RGC alterations. Additionally, downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in both the retinal tissues and RGCs, whereas the silencing of miR-149 was observed to promote the viability of RGC and inhibit RGC apoptosis. Taken together, the results of the current study provided validation suggesting that the downregulation of miR-149 confers protection to RGCs by means of activating the PI3K/Akt signaling pathway via upregulation of BTC in mice with glaucoma. Evidence presented indicated the promise of miR-149 inhibition as a potential therapeutic strategy for glaucoma treatment.

[Analysis on Clinical Characteristic and Risk Factors of Patients Coexistence of Cerebral Artery Stenosis with Unruptured Intracranial Aneurysm].

OBJECTIVE: To analyze the incidence of intracranial unruptured aneurysms in patients with intracranial artery stenosis,clinical features,and investigate the risk factors for unruptured intracranial aneurysms. METHODS: Medical records from all patients performed with digital subtraction angiography (DSA) who had been treated at Peking University Third Hospital,China,from January 2012 to December 2015 were retrospectively reviewed to identify cases coexistence with cerebral artery stenosis and unruptured intracranial aneurysm. RESULTS: Of 273 patients with cerebral artery stenosis (≥50%),intracranial unruptured aneurysms was observed in 17 cases (6.23%) from age of 45 to 78,among them 8 (47.06%) were female and 9 (52.94%) were male. The incidence of unruptured intracranial aneurysm in male patients was 4.17% (9/216),and that of female was 14.4% (8/57). There was statistically significant difference between the male and female incidence of intracranial aneurysm ( P<0.05). Of these 17 patients,16 (94.12%) aneurysms were located in the internal carotid artery (ICA) system,1 (5.88%) aneurysm was located at the tip of the basilar artery. In 11 cases (64.71%),aneurysms were located at the distal of the stenotic vessels,2 (11.76%) were located at the proximal of the stenotic vessels,and 4 cases (23.53%) of which the aneurysm and stenosis were not in the same artery. Logistic multivariate analysis showed that gender was an independent risk factor for aneurysms in patients with cerebral arterial stenosis. CONCLUSION: In the intracranial artery stenosis atients,the possibility of the occurrence of the aneurysm is much higher than the general population,and women were more prominent than man. Sex is an independent risk factor for aneurysms in patients with cerebral arterial stenosis.

[Expression of microRNA-29b in mice with amyotrophic lateral sclerosis].

OBJECTIVE: To investigate microRNA-29b (miR-29b) expression in cerebral cortex, spinal cord, fore limb muscle, and serum of SOD1-G93A amyotrophic lateral sclerosis (ALS) mice, and to identify the biomarker and to assess diagnostic values for ALS. METHODS: Cerebral cortex, spinal cord, fore limb muscle and serum from 16 SOD1-G93A ALS mice and 16 wild-type mice were taken and then microRNA extracted, detecting the expression of miR-29b by real-time quantitative polymerase chain reaction (RT-qPCR). The diagnostic performance of miR-29b for ALS was estimated by the receiver operating characteristic (ROC) curve. RESULTS: The results from the validation indicated that the differences in miR-29b between the cerebral cortex of SOD1-G93A ALS and the healthy control subjects were statistically significant (P=0.001). Meanwhile, the expressions 8, 12, and 16 weeks later were higher than those of the controls (ALS vs. CONTROL: 8 weeks, P=0.044; 12 weeks, P=0.018; 16 weeks, P=0.045). When the relative expression level of miR-29b was used to diagnose ALS in SOD1-G93A ALS mice, the area under the ROC (area under the curve, AUC) was 0.885, if the diagnostic threshold was set at 0.185 6, the sensitivity and specificity were 92.9% and 71.4%. CONCLUSION: miR-29b may act as medical monitoring indices of ALS in early time.

Regulation of nuclear TDP-43 by NR2A-containing NMDA receptors and PTEN.

The dysfunction of TAR DNA-binding protein-43 (TDP-43) is implicated in neurodegenerative diseases. However, the function of TDP-43 is not fully elucidated. Here we show that the protein level of endogenous TDP-43 in the nucleus is increased in mouse cortical neurons in the early stages, but return to basal level in the later stages after glutamate accumulation-induced injury. The elevation of TDP-43 results from a downregulation of phosphatase and tensin homolog (PTEN). We further demonstrate that activation of NR2A-containing NMDA receptors (NR2ARs) leads to PTEN downregulation and subsequent reduction of PTEN import from the cytoplasm to the nucleus after glutamate accumulation. The decrease of PTEN in the nucleus contributes to its reduced association with TDP-43, and thereby mediates the elevation of nuclear TDP-43. We provide evidence that the elevation of nuclear TDP-43, mediated by NR2AR activation and PTEN downregulation, confers protection against cortical neuronal death in the late stages after glutamate accumulation. Thus, this study reveals a NR2AR-PTEN-TDP-43 signaling pathway by which nuclear TDP-43 promotes neuronal survival. These results suggest that upregulation of nuclear TDP-43 represents a self-protection mechanism to delay neurodegeneration in the early stages after glutamate accumulation and that prolonging the upregulation process of nuclear TDP-43 might have therapeutic significance.

[Acoustic analysis for 21 patients with amyotrophic lateral sclerosis complaining of dysarthria].

OBJECTIVE: To observe the characteristics of acoustic parameters of 21 patients with amyotrophic lateral sclerosis (ALS) complaining of dysarthria and to explore the possibility and clinical value of Multi-Dimensional Voice Program (MDVP) on aseessing the patient's voice. METHODS: The clinical data and speech intelligibility of each of the 21 patients with ALS complaining of dysarthria were collected. All the 21 patients with ALS and 44 normal subjects were suggested to pronounce the vowel [a:]. The voice samples were collected and analyzed by Multi Dimensional Voice Program. The data were compared to detect the difference between the two groups. RESULTS: Speech intelligibility of 10 in the 21 patients was above 97% including 5 patients whose scores were 100%. It seemed that the speech intelligibility score was not related with the duration of the disease and the on-set part. The values of noise to harmonic ratio (NHR) of both the light and the severe damage to the speech group were higher than those of the control group with significant difference (P<0.05).Significant difference was noticed between the severe damage to the speech group and control group in Jitter. CONCLUSION: Multi Dimensional Voice Program could be used to analyze the characteristics of acoustic parameters of patients with ALS patients complaining of dysarthria. There was more noise composition in the voice of the patients with dysarthria. NHR seemed to be the sensitive and stable parameter. Especially in patients whose speech intelligibility were affected severely, more acoustic parameters were detected with significant difference.

Penthorum chinense Pursh inhibits ferroptosis in cellular and Caenorhabditis elegans models of Alzheimer's disease.

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.

[The characteristics of anorectal manometry in Parkinson's disease with constipation and functional constipation].

OBJECTIVE: To investigate the discrepancy of anorectal function in patients of Parkinson's disease (PD) with constipation and functional constipation (FC). METHODS: Fifteen consecutive male PD patients with constipation and 45 male FC patients were recruited for the study. All subjects underwent colonoscopy or barium enema in order to exclude organic colon diseases. Every patient underwent anorectal manometry and was categorized into subgroups of either dyssynergia defecation (F3a) or inadequate defecatory propulsion (F3b). RESULTS: The ages of PD with constipation and FC patients were (70 ± 11) and (68 ± 11) years old respectively. The rectal resting pressure in PD with constipation was higher than that in FC group without statistical significance [9.0(4.0, 15.0) mm Hg vs 6.0(3.0, 9.5) mm Hg, P = 0.082, 1 mm Hg = 0.133 kPa]. The anal resting pressure in PD group was not different from FC group [(51.2 ± 17.2) mm Hg vs (59.7 ± 20.4) mm Hg, P = 0.152]. During anal squeezing, the maximal contraction pressure and area under the squeeze curve in PD with constipation group were both significantly lower than FC patients [maximal contraction pressure: (136.9 ± 43.8) mm Hg vs (183.0 ± 62.1) mm Hg, P = 0.010; area under the squeeze curve: (823.5 ± 635.7) mm Hg·s vs (1392.4 ± 939.9) mm Hg·s, P = 0.033]. During forced defecation, both of the defecation rectal pressure and defecation anal pressure in PD with constipation group were significantly lower than that of FC patients [22.0(15.0, 30.0) vs 42.0(31.0, 55.0) mm Hg, P = 0.000; and (46.3 ± 23.3) vs (77.9 ± 35.1) mm Hg, P = 0.002]. The proportions of F3a subtype were 10/15 and 46.7% (21/45) in PD with constipation and FC patients respectively. There was no significant difference in the constituent ratio (P = 0.120). Initial rectal sensory volumes were (91.3 ± 56.9) ml and (67.2 ± 38.9) ml in PD with constipation and FC patients respectively. Even both volumes were higher than the normal controls, there was no significant difference between the two groups (P = 0.074). CONCLUSIONS: Both PD with constipation and FC patients have abnormal anorectal motility and sensation comparing to the FC group, the parameters of anal contraction and defecation are significantly lower, F3b is dominant, and rectal sensory threshold is higher in PD with constipation patients. These parameters could possibly characterize the anorectal manometry for PD with constipation patients, which is helpful to understand the pathogenesis of PD and differentiate from other diseases.

[Clinical and neuro electrophysiologic study of flail arm syndrome].

OBJECTIVE: To explore the clinical and neuroelectrophysiological characteristics of flail arm syndrome (FAS). METHODS: The clinical and neuroelectrophysiological characteristics were analyzed retrospectively from July 1, 2006 to July 1, 2012 in FAS patients (n = 56), those with upper limb onset amyotrophic lateral sclerosis (ALS) (n = 60) and those with upper brachial plexus neuropathy (n = 22) from our hospital. Nerve conduction study of musculocutaneous, axillary, median, ulnar, radial, tibial, peroneal and sural nerves and electromyogram (EMG) of bulbar, cervical, thoracic and lumbosacral regions were conducted. RESULTS: In FAS patients, the ratio of male-to-female was 5:1 and they were characterized by symmetric, proximal wasting and weakness of upper extremities, the involved muscles demonstrated neurogenic damage on EMG and the amplitude of compound muscle action potential (CMAP) of arms decreased. Compared with ALS patients, the amplitude of motor unit action potential (MUAP) of deltoid muscle and biceps muscle was higher in FAS patients ((1531 ± 76) vs (898 ± 57) µV; (1433 ± 57) vs (872 ± 75) µV) (F = 13.25, 6.33; P < 0.05). Compared with upper brachial plexus neuropathy patients, the amplitude of MUAP of first dorsal interosseous, deltoid and biceps muscles was higher in FAS patients ((1263 ± 24) vs (507 ± 42) µV; (1531 ± 76) vs (564 ± 27) µV; (1433 ± 57) vs (593 ± 36) µV) (F = 12.32, 16.71, 8.35; P < 0.05). CONCLUSION: The clinical manifestations of FAS are symmetric, proximal wasting and weakness of arms. And the involved muscles show denervation on EMG and the amplitudes of CMAPs decrease in motor nerves of upper extremities.

[Clinical and neurophysiologic profiles of sensory neuron disease].

OBJECTIVE: To explore the clinical and electrophysiological characteristics of sensory neuron disease (SND). METHODS: The clinical and electrophysiological characteristics were analyzed from November 2007 to November 2012 in 57 patients with sensory neuron disease and another 95 with sensory polyneuropathy. Nerve conduction studies of median nerve, ulnar nerve, tibial nerve, peroneal nerve and sural nerve and electromyogram (EMG) of bulbar, cervical, thoracic and lumbosacral region, somatosensory evoked potential (SEP) and contact heat evoked potential (CHEP) were performed. RESULTS: The amplitude of sensory nerve action potential (SNAP) decreased in 50 SND patients and disappeared in another 7. The parameters of SEP and CHEP were abnormal. The amplitude of SNAP was lower in median and ulnar nerve than in sural nerve ((0.6 ± 0.2) µV, (0.7 ± 0.2) µV vs (1.5 ± 0.5) µV; t = 2.42, 2.38; P < 0.05). The latencies of SEPs were longer in SND patients than in those with sensory polyneuropathy (t = 1.99, 1.99, 2.00, 2.07, 1.99; 1.98, 1.99, 2.02, 1.98, 1.99; P < 0.05).Comparing with those with sensory polyneuropathy, the latencies of CHEP were longer in SND patients when the stimuli was applied at hand dorsum, proximal volar forearm and anticus tibialis (t = 2.01, 2.00, 2.02; P < 0.05). No difference existed in latencies between 2 groups when the stimuli was at the levels of C7 and T12 (t = 0.97, 0.68; P > 0.05). CONCLUSION: Sensory neuron diseases usually present with sensory symptoms and ataxia. The amplitude of SNAP decreases or disappears especially in upper extremities. Both SEP and CHEP are abnormal.

Promising application of a new ulnar nerve compound muscle action potential measurement montage in amyotrophic lateral sclerosis: a prospective cross-sectional study.

Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional "belly-tendon" montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles. A new method of ulnar nerve compound muscle action potential measurement was developed in 2020, which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist. This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential. In this prospective cross-sectional study, we included 64 patients with amyotrophic lateral sclerosis and 64 age- and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital. The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage. In the controls, no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings. In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy, the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2 (P < 0.01). Using the new method, damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method, in particular for patients in early stage amyotrophic lateral sclerosis. In addition, the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position, and that this method is more suitable for monitoring disease progression than the traditional montage. This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.

Targeting autophagy to discover the Piper wallichii petroleum ether fraction exhibiting antiaging and anti-Alzheimer's disease effects in Caenorhabditis elegans.

BACKGROUND: With population aging, the incidence of aging-related Alzheimer's disease (AD) is increasing, accompanied by decreased autophagy activity. At present, Caenorhabditis elegans (C. elegans) is widely employed to evaluate autophagy and in research on aging and aging-related diseases in vivo. To discover autophagy activators from natural medicines and investigate their therapeutic potential in antiaging and anti-AD effects, multiple C. elegans models related to autophagy, aging, and AD were used. METHOD: In this study, we employed the DA2123 and BC12921 strains to discover potential autophagy inducers using a self-established natural medicine library. The antiaging effect was evaluated by determining the lifespan, motor ability, pumping rate, lipofuscin accumulation of worms, and resistance ability of worms under various stresses. In addition, the anti-AD effect was examined by detecting the paralysis rate, food-sensing behavior, and amyloid-ß and Tau pathology in C. elegans. Moreover, RNAi technology was used to knock down the genes related to autophagy induction. RESULTS: We discovered that Piper wallichii extract (PE) and the petroleum ether fraction (PPF) activated autophagy in C. elegans, as evidenced by increased GFP-tagged LGG-1 foci and decreased GFP-p62 expression. In addition, PPF extended the lifespan and enhanced the healthspan of worms by increasing body bends and pumping rates, decreasing lipofuscin accumulation, and increasing resistance to oxidative, heat, and pathogenic stress. Moreover, PPF exhibited an anti-AD effect by decreasing the paralysis rate, improving the pumping rate and slowing rate, and alleviating Aß and Tau pathology in AD worms. However, the feeding of RNAi bacteria targeting unc-51, bec-1, lgg-1, and vps-34 abolished the antiaging and anti-AD effects of PPF. CONCLUSION: Piper wallichii may be a promising drug for antiaging and anti-AD. More future studies are also needed to identify autophagy inducers in Piper wallichii and clarify their molecular mechanisms.

[Radiological imaging in evaluation of etiologies for cerebral infarction after non-cardiac surgeries].

OBJECTIVE: To investigate the pathogenesis of cerebral infarction after non-cardiac surgeries according to imaging. METHODS: Retrospective analyses of clinical and imaging data of 17 patients with postoperative cerebral infarction (average 68 years old, total incidence 0.049%) from departments of orthopedics and general surgery were conducted during 52 months. RESULTS: Cerebral infarction occurred 39.1 hours after operation on average. Among the 17 patients, eight were detected with disturbance of consciousness, ten with hemiplegia, six with speech disorder and two with unilateral sensory disturbance. Six (35.3%) had blood lipids tests. Five (29.4%) had neck vascular ultrasound and one had intracranial magnetic resonance angiography (MRA). When discharged, one patient was declared death and ten had impaired neurological function in various degrees. Among six patients with previous stroke, one (16.7%) received neurological consultation before surgery. According to the image manifestation, ten cases were territory circulation infarcts, four centrum ovale infarcts and three watershed infarcts. CONCLUSIONS: This study suggests that total incidence of cerebral infarction after non-cardiac surgeries is lower than previously reported and there is greater involvement of atherosclerosis. Patients' conditions should be closely observed within at least four days after surgeries. Preoperative assessment should be strengthened in order to avoid occurrence of postoperative cerebral infarction.

[The relation between plasma homocysteine level and amyotrophic lateral sclerosis].

OBJECTIVE: To investigate the relationship between plasma level of homocysteine (Hcy) and amyotrophic lateral sclerosis (ALS). METHODS: The differences of Hcy, Vitamin B(12), and folate levels between 150 outpatients with ALS and 137 age and sex matched controls were compared in a cross-sectional study. RESULTS: Compared with the healthy controls, patients with ALS had a higher plasma Hcy level [(18.47 ± 13.09) µmol/L vs (11.91 ± 5.37) µmol/L, P < 0.001] and a lower folate level [(8.39 ± 4.45) ng/ml vs (10.38 ± 5.01) ng/ml, P < 0.001]. In a logistic regression model using ALS as a dependent variable, plasma level of Hcy was significantly associated with ALS. A trend for higher Hcy levels in patients with shorter interval from symptom onset to diagnosis (ODI) was also found [Hcy levels (20.73 ± 15.79) µmol/L with ODI < 19 months vs (16.41 ± 9.73) µmol/L with ODI ≥ 19 months, P = 0.035]. CONCLUSIONS: Plasma Hcy level is significantly increased in patients with ALS. The individuals with shorter time to diagnosis present higher Hcy level, suggesting that it may associate with the progression pace of ALS.

[A study of motor unit number estimation by multiple point stimulation in patients with Hirayama disease].

OBJECTIVE: To explore the significance of motor unit number estimation (MUNE) by using multiple point stimulating technique to evaluate patients with Hirayama disease (HD). METHODS: Multiple point stimulating technique was used to estimate the motor unit number of abductor pollicis brevis and abductor digiti minimi in 35 normal subjects [14 - 33 years old, mean (20.9 ± 4.0) years old, 33 men and 2 women] without nerve and muscle disease and 69 patients definitely diagnosed as HD [16 - 35 years old, mean (21.46 ± 6.61) years old, 67 men and 2 women]. The differences between the two groups were examined by Fisher's exact test and t test. RESULTS: There were 42 patients with atrophy and 27 patients with normal clinical manifestation of left hand. For right hand there were 54 patients with atrophy and 15 normal. For controls, the MUNE value of left abductor pollicis brevis was 226.97 ± 30.59, while that of right side was 228.31 ± 25.35. The MUNE value of left abductor digiti minimi was 237.43 ± 30.78, while that of right side was 240.20 ± 37.73. For HD patients, the MUNE of left abductor pollicis brevis and abductor digiti minimi was 145.66 ± 126.10 (t = 5.07, P < 0.01) and 102.20 ± 112.67 (t = 9.31, P < 0.01) respectively, while those of right hand was 149.72 ± 117.80 (t = 5.31, P < 0.01) and 64.23 ± 69.27 (t = 16.76, P < 0.01) respectively. MUNE of left abductor digiti minimi in 17 patients that was below 200 among 27 patients with normal clinical manifestation (χ(2) = 9.57, P = 0.002). MUNE of right abductor digiti minimi in 12 patients that was below 200 among 15 patients with normal clinical manifestation (χ(2) = 4.64, P = 0.03). CONCLUSIONS: The differences of MUNE values by multiple point stimulating technique between the normal subjects and the HD patients is significant, which suggests this method is very useful to evaluate HD in the early state.

[Hyperdense middle cerebral artery sign among patients with severe ischemic attack on ultra-early phase].

OBJECTIVE: To detect the frequency of hyperdense middle cerebral artery sign (HMCAS) among patients with severe ischemic attack (baseline NIHSS score ≥ 10) in the middle cerebral artery (MCA) territory within 3 hours after onset and compare the baseline characteristics and 90-day outcomes between the HMCAS (+) and HMCAS (-) groups. METHODS: A total of 43 patients were evaluated with baseline clinical characteristics, laboratory tests and brain CT/MRI. Follow-up evaluation at the end of 90 days included the modified Rankin Scale (mRS), the Bathel Index (BI) and death. RESULTS: Ten out of forty-three (23.3%) patients were HMCAS (+).The 24-hour NIHSSS of HMCAS (+) group was significantly higher than that of HMCAS (-) group (20.2 ± 5.4 vs. 14.8 ± 7.2, P= 0.037). The follow-up scanning confirmed that all HMCAS (+) patients had larger MCA territory infarction and the ratio of large MCA territory infarction was significantly higher than that of HMCAS (-) group (100% vs. 39.1%, P = 0.001). There were no significant differences in age, gender, risk factors, time intervals, laboratory tests, 90-day functional outcomes between the two groups. CONCLUSION: The HMCAS (+) patients had notable deterioration 24 hours after onset and had more severe MCA infarction. HMCAS detected by non-enhanced CT at admission should be considered as an alarming sign among patients with severe neurological deficit of MCA territory infarction.

[Diagnostic role of triple stimulation technique in patients with multifocal motor neuropathy].

OBJECTIVE: To detect the conduction block (CB) between nerve root and Erb's point by triple stimulation technique (TST) in patients with multifocal motor neuropathy (MMN). METHODS: The subjects were recruited from Peking University Third Hospital during the period of April 2010 to April 2011. Twelve MMN patients, 30 healthy subjects, 30 patients with cubital tunnel syndrome and 30 patients with amyotrophic lateral sclerosis (ALS) underwent TST along with clinical assessments and nerve conduction studies. TST combined transcranial magnetic stimulation (TMS) of motor cortex with peripheral collision studies. The results were expressed by the TST amplitude ratio. And the conduction block was judged by TST amplitude ratio or the amplitude ratio of compound muscle action potential (CMAP). RESULTS: The TST amplitude ratio of healthy volunteers was 93.0% ± 2.7%. And it was 42.3% ± 7.1% in patients with MMN indicating a proximal CB. There were 47 CBs in distal segments by routine nerve conduction study. Compared with the baseline levels, the patients with definite MMN increased (χ(2) = 6.31, P < 0.05). The TST amplitude ratio (30.5% ± 4.8%) of those with ALS indicated the lesion of pyramid tract (t = 2.43, P < 0.05). And the TST amplitude ratio (92.2% ± 2.6%) of those with cubital tunnel syndrome was normal (t = 0.68, P > 0.05) while the nerve conduction velocity of cubital tunnel syndrome patients (below elbow-above elbow) was slower ((23.6 ± 3.5) m/s) (t = 2.00, P < 0.05). CONCLUSION: TST may be used to detect proximal CB and facilitate the diagnosis of MMN.