Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

BACKGROUND: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. CONCLUSION: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

Efgartigimod in the treatment of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré Syndrome (GBS) is caused by immunoglobulin G (IgG) autoantibodies. Efgartigimod, a human IgG antibody Fc fragment that acts as a natural ligand for the FcRn, can increase IgG degradation, which thus may be a promising therapeutic drug for GBS. CASE PRESENTATION: The two patients presented with postinfectious and acute flaccid paralysis. On admission, they were bedridden. Nerve conduction studies indicated peripheral neuropathy. GBS was suspected and they are treated with two doses of efgartigimod (10 mg/kg) within 5 days. Their muscle strength improved gradually and 4 weeks after the initial dose, they could walk independently. Following the first dose, Patient 1 complaint of muscle soreness, which subsided the next morning. Patient 2 was intubated due to respiratory failure the day after the initial dose, and did not report other adverse effects. DISCUSSION: In GBS patients, two doses of efgartigimod (10 mg/kg) were effective in rapidly improving muscle strength, with a satisfactory safety profile. The findings suggest a potential role for efgartigimod in modifying the disease process in GBS patients. CONCLUSION: Efgartigimod seems effective and safe in the treatment of GBS. This study indicates the potential role of efgartigimod as a novel treatment option for GBS. Well-designed clinical trials should be conducted.

Constructing and Validating a Nomogram Model for Short-Term Prognosis of Patients with AChR-Ab+ GMG.

OBJECTIVE: This study aimed to establish and validate a nomogram prognostic model for predicting short-term efficacy of acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (GMG). METHODS: A retrospective observational study was conducted at the First Hospital of Shanxi Medical University, enrolling patients diagnosed with AChR-Ab+ GMG from May 2020 to September 2022. The primary outcome was the change in the Myasthenia Gravis Foundation of America (MGFA) post-intervention status after 6 months of standard treatment. Predictive factors were identified through univariate and multivariate logistic regression analyses, with significant factors incorporated into the nomogram. The bootstrap test was used for internal validation of the nomogram model. Model performance was assessed using calibration curves, receiver-operating characteristic curve analysis, and decision curve analysis (DCA). RESULTS: A total of 90 patients were enrolled, of whom 30 achieved unchanged or worse status after 6 months of standard therapy. Univariate logistic regression analysis showed that quantitative myasthenia gravis score, gender, body mass index, course of disease, hemoglobin levels, and white blood cell counts were six potential predictors. These factors were used for multivariate logistic regression analysis, and a nomogram was constructed. The calibration curve showed that the predicted value was in good agreement with the actual value (p = 0.707), and the area under the curve value (0.792, 95% CI 0.686-0.899) indicated good discrimination ability. DCA suggests that this model has potential clinical application value. CONCLUSION: The constructed nomogram, based on key patient indicators, shows promise as a clinically useful tool for predicting the short-term efficacy of treatment of AChR-Ab+ GMG. Validation in larger, multicenter cohorts is needed to further substantiate its applicability.

The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis.

BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally. METHODS: In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR. RESULTS: Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies (I2 = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05). CONCLUSIONS: Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.

Diaphragmatic ultrasonography as a predictor of respiratory muscle fatigue in myasthenia gravis.

INTRODUCTION/AIMS: Easy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients. METHODS: GMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N-TFdi and N-Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax. RESULTS: Thirty-four GMG patients and 30 healthy controls were enrolled. N-TFdi and N-Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15. DISCUSSION: DUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.

Promising efficacy of Low-Dose rituximab in Muscle specific kinase antibody positive Myasthenia Gravis.

AIMS: The study aims to evaluate the efficacy of low dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). METHODS: This is a single-center, retrospective study. A total of 10 patients with MuSK-MG were admitted to the Department of Neurology, First Hospital, Shanxi Medical University, between April 2021 to April 2023. Of them, 9 patients had been treated with low dose RTX (500 mg every 6 month) and recruited in this study. The clinical information, including the severity before and after RTX treatment, were collected from the medical records. Clinical effectiveness was assessed by Myasthenia Gravis Foundation of America (MGFA)-postintervention status (PIS), MG-related activities of daily living (MG-ADL), Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r), dosage of steroid at the end of follow up. RESULTS: All nine patients showed clinical improvement at the final follow-up after low-dose RTX treatment. The mean dose of prednisolone decreased significantly from 50 mg at baseline to 18.33 mg at the last follow-up (z = -3.417, p = 0.001). The administration of low-dose RTX treatment led to significant improvements in ADL levels (Z = -2.675, P < 0.01), QMG score levels (Z = -2.371, P < 0.05) and QOL-15r levels (Z = -2.547, P < 0.01) at last visit. CONCLUSION: Low-dose RTX is effective for treating MuSK-MG patients. Longer-term follow-up and larger-scale studies are needed to provide further evidence.

A novel autosomal dominant ERLIN2 variant activates endoplasmic reticulum stress in a Chinese HSP family.

OBJECTIVE: Hereditary spastic paraplegia (HSP) has been reported rarely because of a monoallelic variant in ERLIN2. The present study aimed at describing a novel autosomal dominant ERLIN2 pedigree in a Chinese family and exploring the possible mechanism of HSP caused by ERLIN2 variants. METHODS: The proband and his family underwent a comprehensive medical history inquiry and neurological examinations. Whole-exome sequencing was performed on the proband, and Sanger sequencing was performed on some family members. HeLa cell lines and mouse primary cortical neurons were used for immunofluorescence (IF) and reverse transcription-PCR (RT-PCR). RESULTS: Seven patients were clinically diagnosed with pure spastic paraplegia in four consecutive generations with the autosomal dominant inheritance model. All patients presented juvenile-adolescent onset and gradually worsening pure HSP phenotype. Whole-exome sequencing of the proband and Sanger sequencing of all available family members identified a novel heterozygous c.212 T>C (p.V71A) variant in exon 8 of the ERLIN2 gene. The c.212 T>C demonstrated a high pathogenic effect score through functional prediction. RT-PCR and IF analysis of overexpressed V71A revealed an altered ER morphology and increased XBP-1S mRNA levels, suggesting the activation of ER stress. Overexpression of V71A in primary cultured cortical neurons promoted axon growth. INTERPRETATION: The novel c.212 T>C heterozygous variant in human ERLIN2 caused pure HSP. Moreover, c.212 T>C heterozygous variant in ERLIN2 increased ER stress and affected axonal development.

Hyperhomocysteinemia in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

INTRODUCTION/AIMS: Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy. METHODS: We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants. RESULTS: The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20. DISCUSSION: HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.

Diagnostic utility of different dysphagia screening tools to detect dysphagia in individuals with amyotrophic lateral sclerosis.

OBJECTIVE: Dysphagia is a common and serious clinical symptom of amyotrophic lateral sclerosis (ALS). The study aimed to evaluate the diagnostic utility of four dysphagia screening tools in ALS, including the ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subscale, water-swallowing test (WST), Eating Assessment Tool-10 (EAT-10) and Sydney Swallow Questionnaire (SSQ). METHODS: A total of 68 individuals from First Hospital, Shanxi medical university, were recruited in the study. The ALSFRS-R, WST, EAT-10, SSQ and the gold standard video fluoroscopic swallowing study (VFSS) were performed. The Penetration Aspiration Scale (PAS) during VFSS was assessed to identify unsafe swallowing (PAS ≥ 3) and aspiration (PAS ≥ 6). Receiver operator characteristic curve (ROC) analyses were performed to evaluate the accuracy of the 4 tools. Youden index was used to determine the ideal cut-off value for each tool. RESULTS: Of the patients, 20.59% (14/68) presented unsafety swallowing and 16.18% (11/68) had aspiration. The four tools could effectively identify patients with unsafe swallowing and aspiration. The EAT-10 had the maximum AUC (0.873 and 0.963, respectively) among the tools in the diagnosis of unsafe swallowing and aspiration. To detect unsafe swallowing and aspiration, an EAT-10 score of 6 (sensitivity: 78.6%, specificity: 87.0%) and an EAT-10 score of 8 (sensitivity: 90.9%, specificity: 91.2%), were the most appropriate cut-off points, respectively. CONCLUSIONS: The ALSFRS-R bulbar subscale, WST, EAT-10, and SSQ could effectively identify unsafe swallowing and aspiration in patients with ALS. Of the four tools, the EAT-10 was relatively accurate, safe, and convenient. Further studies including more patients should be conducted to verify the conclusions.

Effects of aspect on phenology of Larix gmelinii forest in Northeast China.

The response of vegetation phenology to global climate change is one of the main forms in terrestrial ecosystem change, the study of vegetation phenology is an important complement to the understanding of how global climate change affects ecosystems in multiple dimensions. We selected the distribution area of Larix gmelinii in The Greater Khingan Mountains as a case area by eliminating the heterogeneity of vegetation types, with the support of Google Earth Engine platform, we studied the effects of different aspects and land surface temperature (LST) on remote sensing phenology (RSP) that is defined as start of growing season (SOS), end of growing season (EOS) and length of growing season (LOS) respectively in the study area through Normalized Difference Vegetation Index (NDVI) changes. The results showed that SOS advanced in different aspects during the study period, and the advance amplitude of SOS on the east and west aspect was greater than that on the south and north. Except for the east aspect, EOS showed a slight postponed, and LOS was prolonged on all aspects. The latitude difference between 51° and 53° N had no significant effect on L. gmelinii in different aspects. LST had an obviously direct effect on the RSP of L. gmelinii in different aspects, and the effect of LST on SOS and LOS was significantly greater than that on EOS. The effect of LST on SOS and LOS was significant in April and spring. The main contributor to the increase of LOS was the advance of SOS, while the postponed of EOS has a relatively small contribution to LOS. Due to the redistribution of meteorological factor by aspect, the spatial and temporal heterogeneity of RSP tends to be complex, so determining the same aspect is one of the main ways to reduce the phenological heterogeneity in the study of vegetation RSP.

Data-independent acquisition-based quantitative proteomic analysis of m.3243A>G MELAS reveals novel potential pathogenesis and therapeutic targets.

The pathogenesis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) syndrome has not been fully elucidated. The m.3243A > G mutation which is responsible for 80% MELAS patients affects proteins with undetermined functions. Therefore, we performed quantitative proteomic analysis on skeletal muscle specimens from MELAS patients. We recruited 10 patients with definitive MELAS and 10 age- and gender- matched controls. Proteomic analysis based on nanospray liquid chromatography-mass spectrometry (LC-MS) was performed using data-independent acquisition (DIA) method and differentially expressed proteins were revealed by bioinformatics analysis. We identified 128 differential proteins between MELAS and controls, including 68 down-regulated proteins and 60 up-regulated proteins. The differential proteins involved in oxidative stress were identified, including heat shock protein beta-1 (HSPB1), alpha-crystallin B chain (CRYAB), heme oxygenase 1 (HMOX1), glucose-6-phosphate dehydrogenase (G6PD) and selenoprotein P. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis showed significant enrichment in phagosome, ribosome and peroxisome proliferator-activated receptors (PPAR) signaling pathway. The imbalance between oxidative stress and antioxidant defense, the activation of autophagosomes, and the abnormal metabolism of mitochondrial ribosome proteins (MRPs) might play an important role in m.3243A > G MELAS. The combination of proteomic and bioinformatics analysis could contribute potential molecular networks to the pathogenesis of MELAS in a comprehensive manner.

GGC repeat expansions in NOTCH2NLC causing a phenotype of lower motor neuron syndrome.

A genetic diagnosis cannot be made in a considerable proportion of patients with hereditary lower motor neuron (LMN) syndromes. The GGC repeat expansion in the 5'untranslated region (5'UTR) of NOTCH2NLC gene has been reported to be associated with a group of NOTCH2NLC-related repeat expansion disorders (NRED), including amyotrophic lateral sclerosis (ALS). The relationship between the mutation and LMN syndromes has not been reported previously. Here, we identified the GGC repeat expansions of NOTCH2NLC in a Chinese familial patient with LMN syndrome, presenting with slowly progressive weakness of four limbs. Needle electromyography revealed evidence of acute denervation and chronic neurogenic changes. Cognition and brain MRI were normal. Initial whole-exome sequencing by next generation sequencing revealed negative results. However, repeat-primed polymerase chain reaction performed on the proband showed a pathogenic GGC expansion in the 5'UTR of NOTCH2NLC and long-read sequencing subsequently revealed 248 GGC repeats. The mutation was co-segregated with the clinical phenotype in the family. Immunofluorescent studies identified p62-positive protein deposits in the intranuclear inclusions in myofibers. The GGC repeat expansion in NOTCH2NLC is associated with a new phenotype of hereditary LMN syndrome. As a result, NOTCH2NLC genotyping should be performed in patients with hereditary LMN syndromes.

Neuromuscular junction disorders: Experimental models and pathophysiological mechanisms.

Located between skeletal muscle fibers and motoneurons, the neuromuscular junction is a chemical synapse essential for the transmission of information from nervous system to skeletal muscle. There are many diseases related to neuromuscular junction dysfunction, including myasthenia gravis, Lambert­Eaton myasthenic syndrome, congenital myasthenic syndromes, amyotrophic lateral sclerosis, and spinal muscular atrophy. The pathophysiological mechanisms of these diseases have been investigated using many animal models. Among them, mouse models are the most commonly used and have provided the majority of current data. Moreover, advances in human induced pluripotent stem cell technology has resulted in new opportunities to study neuromuscular junction disorders from both patients and healthy individuals. Currently, patient­specific induced pluripotent stem cells derived from motor neurons have begun to be studied. These studies will help us achieve a more comprehensive understanding of diseases related to neuromuscular junction disorders. We will describe the research models of neuromuscular junction disorders and provide an overview of recent key findings.

Neurofilament markers in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

This study aims to determine the serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) in amyotrophic lateral sclerosis (ALS) patients, and to explore their feasibility as valid biomarkers for quantifying disease progression and predicting individual prognosis. 52 patients with ALS and 30 controls with noninflammatory neurological diseases were included. NFL and pNFH levels in serum and CSF were measured by enzyme-linked immunosorbent assay. Our findings showed that serum and CSF levels of NFL and pNFH in ALS patients were significantly increased. These values were negatively correlated with disease duration (except CSF NFL with disease duration) and ALSFRS-r score, and positively correlated with disease progression rate (DPR) and upper motor neuron (UMN) score, but did not correlate with bilateral median and ulnar nerve compound muscle action potential (cMAP) amplitudes (except a weak correlation between CSF NFL and cMAP amplitudes). The optimal cut-off values with high sensitivity and specificity were obtained in ROC curve analysis to discriminate ALS from controls. Kaplan-Meier survival curves illustrated that survival was significantly shorter for patients with higher neurofilament levels at diagnosis. The Cox proportional hazards regressions confirmed that NFL and pNFH were significant predictors of survival. Overall, NFL and pNFH in serum and CSF can be used as reliable biomarkers in ALS.

Genetic analysis in Chinese patients with familial or young-onset amyotrophic lateral sclerosis.

OBJECTIVE: The aim of our study was to investigate the genetic characteristics in patients with familial or young-onset amyotrophic lateral sclerosis (ALS) in a Chinese center. METHODS: Patients with familial or young-onset (age of onset < 45 years old) ALS were reviewed. The clinical data was collected. Whole-exome sequencing was performed to identify the disease-associated variants. Single-nucleotide variants and small insertions/deletions were further predicted with silico tools and compared to the Single Nucleotide Polymorphism Database, Exome Aggregation Consortium, and the 1000 Genomes Project. The evolutionary conservations were estimated, and the structures of proteins were constructed by Swiss-Model server. Immunohistochemistry was used to confirm the misfolded SOD1 protein. RESULTS: Three familial ALS and 5 young-onset ALS were enrolled. Genetic analysis identified related variants of SOD1 (4/6, 66.7%), FUS (1/6, 16.7%), and NEK1 (1/6, 16.7%) in 6 patients. Three of them were familial probands (3/3, 100%), and the others were sporadic young-onset patients (3/5, 60%). NEK1 c.290G > A mutation (NM_012224.2 exon4) in a patient with familial ALS and SOD1 c.362A > G mutation (NM_000454 exon5) in a young-onset ALS patient were novel. The novel mutations were predicted to be deleterious, affected evolutionarily highly conserved amino acid residue and the formation of hydrogen bonds between the mutated site and its surrounding amino acid residues. Misfolded SOD1 protein was identified in patient with SOD1 c.362A > G mutation. CONCLUSIONS: Two novel mutations were detected in our patients. Patients with familial or young-onset ALS often carried related gene mutations, and genetic sequencing should be thus routinely performed.

Spatial Scale Effects of the Relationship between Fractional Vegetation Coverage and Land Surface Temperature in Horqin Sandy Land, North China.

Sandy range land refers to a major component of grassland area types in the semi-arid area of northern China. Monitoring of vegetation and land surface temperature (LST) using remote sensing technology can help determine the degree of desertification in a regional and/or sub regional scale, as in the Horqin Sandy Land selected in this study. Correlation analysis was performed to examine the relationship between the fractional vegetation coverage (FVC) and the LST within one growing season (from May to August 2017), at different spatial scales. The results showed that the FVC increased from 0.12 in May to 0.29 in August, and the LST increased first and then declined. The highest LST was 41.68 °C in July, while the lowest was 28.62 °C in August. At the grid scale, the LST increased first and then declined with the increase of the FVC on 25 May, 10 June, and 29 August; the FVC ranged from 0.29-0.38, 0.27-0.32, and 0.29-0.38 with the preference of the 'turning point', respectively. A negative correlation was identified between the FVC and the LST and without any 'turning point' in the fitting curve on 28 July. The correlation between FVC and LST complied with the grid scale at the sample area scale. The coupling analysis of landscape pattern expressed by FVC and LST showed that, the landscape evenness, Euclidean nearest neighbor distance, and landscape splitting degree all showed strong coupling correlation in any study period (P). The landscape aggregation of FVC and LST showed a good coupling at the relatively high and low air temperature conditions of P1 and P3. Landscape contagion showed a good coupling between FVC and LST at relatively moderate air temperature condition of P1 and P4. Air temperature conditions and characteristics of vegetation coverage should be considered for a more targeted analysis when analyzing the relationship between FVC and LST and attention should be paid to the timing and type of study area in practical application.

Pain in acute motor axonal neuropathy.

INTRODUCTION/AIMS: Patients with acute motor axonal neuropathy (AMAN) generally have pure motor neuropathy and clinicians usually do not link pain with AMAN. The aim of this retrospective study was to describe the character, location, and intensity of pain in AMAN and acute inflammatory demyelinating polyneuropathy (AIDP) in the acute phase. METHODS: This was a retrospective study in 44 patients with Guillain-Barré syndrome (GBS) having progressive weakness of more than one limb. The information, including the demographic characteristics, preceding infections, clinical symptoms and signs, severity at nadir, the characteristics of pain, use of analgesics, laboratory and electrophysiological data, and the medical treatment for GBS, were collected from the medical records. RESULTS: In 44 patients, 40.9% were diagnosed as AMAN, and 34.1% as AIDP. Pain was more prevalent in AMAN (76.5%) than in AIDP (26.7%, P = .02). Low back and extremities were the most common locations of pain in AMAN (7/13 and 7/13, respectively) and AIDP (2/4 and 2/4, respectively). DISCUSSION: Pain was a common symptom in AMAN in the acute stage. The presence or absence of pain is not useful for distinguishing AIDP from AMAN.

Fasciculation score: a sensitive biomarker in amyotrophic lateral sclerosis.

OBJECTIVE: The aim of our study was to elucidate the characteristic of fasciculation distributions in amyotrophic lateral sclerosis (ALS) using a fasciculation score (FS) of muscle ultrasound (MUS) and to compare the diagnostic values of three MUS fasciculation parameters in patients. METHODS: Thirty ALS patients, 16 ALS mimics, and 10 healthy subjects were involved. MUS of unilateral 10 muscles in each patient and needle electromyography (EMG) of total 204 muscles were performed to detect fasciculations and spontaneous activity respectively in ALS. Control groups underwent only MUS. Fasciculation was graded semiquantitatively with FS. RESULTS: Three hundred fifty muscles in ALS and 260 in controls were examined. The fasciculation detection rates, total FS, the number of muscles with fasciculation, and the total number of fasciculations in ALS were all significantly higher than those of controls (P < 0.001). ALS patients exhibited a multifocal continuous pattern of fasciculation in limbs, whereas there were few fasciculations in controls. Compared with other parameters, total FS had the largest area under the curve (AUC) (AUC = 0.899, P < 0.001) in ALS diagnosis. The detection rates of lower motor neuron (LMN) acute lesions by MUS (70.6%) and EMG (72.1%) were nearly the same, and a positive correlation between the FS and spontaneous activity grades (P < 0.001, r = 0.359) was proved. CONCLUSIONS: ALS patients exhibited the multifocal continuous pattern of fasciculation in limbs. FS showed high sensitivity and specificity in differentiating ALS from non-ALS patients, and the optimal cut-off value was determined as 4. The combination of MUS and EMG can provide additional information about specific muscles.

A novel Q93H missense mutation in DCTN1 caused distal hereditary motor neuropathy type 7B and Perry syndrome from a Chinese family.

The Dynactin 1 (DCTN1) encodes the p150 subunit of dynactin, which engages retrograde axonal transport. Missense mutations in DCTN1 have been linked to a series of neurodegenerative diseases, including distal hereditary motor neuropathies (dHMN) and Perry syndrome. A few pathogenic DCTN1 mutations related with Perry syndrome have been described within, or adjacent to, the highly conserved N-terminal cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain. But to our best knowledge, only the pathogenic G59S mutation in DCTN1 has been reported in dHMN7B families. Herein, we provided a novel heterozygous mutation in DCTN1 which caused both dHMN7B and Perry syndrome from a Chinese family. Whole exome sequencing (WES) was performed to identify the disease-associated genes. Single nucleotide variants (SNVs) and small insertions/deletions (INDELs) were further predicted with Mutation Taster, Polymorphism Phenotyping v2 (PolyPhen-2), and Sorting Intolerant From Tolerant (SIFT) and compared to the Single Nucleotide Polymorphism Database(dbSNP), Exome Aggregation Consortium (ExAC), and the 1000 Genomes Project. Furthermore, a novel missense mutation c.279G>C (Q93H) in DCTN1 was identified as the candidate loci. The mutation was confirmed with Sanger sequencing in the family members and cosegregated with various phenotypes. In silico analysis and molecular structural modeling, the mutation not only caused the loss of a hydrogen bond within the p150 protein but also affected the formation of hydrogen bonds between p150 and EB. Therefore, the new Q93H mutation in DCTN1 caused both familial dHMN7B and Perry syndrome. Our findings could expand the clinical and pathogenic spectrum and strengthen the clinical diagnostic role of the DCTN1 gene.