The functional implication of ATF6α in castration-resistant prostate cancer cells.

Stress in the endoplasmic reticulum (ER) may perturb proteostasis and activates the unfolded protein response (UPR). UPR activation is frequently observed in cancer cells and is believed to fuel cancer progression. Here, we report that one of the three UPR sensors, ATF6α, was associated with prostate cancer (PCa) development, while both genetic and pharmacological inhibition of ATF6α impaired the survival of castration-resistance PCa (CRPC) cells. Transcriptomic analyses identified the molecular pathways deregulated upon ATF6α depletion, and also discovered considerable disparity in global gene expression between ATF6α knockdown and Ceapin-A7 treatment. In addition, combined analyses of human CRPC bulk RNA-seq and single-cell RNA-seq (scRNA-seq) public datasets confirmed that CRPC tumors with higher ATF6α activity displayed higher androgen receptor (AR) activity, proliferative and neuroendocrine (NE) like phenotypes, as well as immunosuppressive features. Lastly, we identified a 14-gene set as ATF6α NE gene signature with encouraging prognostic power. In conclusion, our results indicate that ATF6α is correlated with PCa progression and is functionally relevant to CRPC cell survival. Both specificity and efficacy of ATF6α inhibitors require further refinement and evaluation.

Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.

BACKGROUND AND PURPOSE: Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. METHODS: Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS). RESULTS: In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. CONCLUSION: Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.

Split Phenomenon of Fasciculation between Antagonistic Muscles in Amyotrophic Lateral Sclerosis: An Ultrasound Study.

OBJECTIVE: Paresis of muscle groups in patients with amyotrophic lateral sclerosis (ALS) tends to present split phenomena. We explored the split phenomenon of fasciculation in multiple antagonistic muscle groups in ALS patients. METHODS: One hundred and forty ALS patients and 66 non-ALS patients were included from a single ALS center. Muscle ultrasonography (MUS) was performed to detect fasciculation in elbow flexor-extensor, wrist flexor-extensor, knee flexor-extensor, and ankle flexor-extensor. Split phenomena of fasciculation between different antagonistic muscle groups were summarized, and the possible influence factors were analyzed through stratified analysis. RESULTS: The frequency of split phenomenon of fasciculation intensity was significantly higher than those of muscle strength (26.1% vs. 7.1% for elbow flexor-extensor, 38.3% vs. 5.7% for wrist flexor-extensor, 37.9% vs. 3.0% for knee extensor-flexor, and 33.6% vs. 14.4% for ankle flexor-extensor) (P < 0.01). For muscles with 0-1 level of muscle strength (the Medical Research Council, MRC, score), significance difference in mean fasciculation intensity was observed only in ankle flexor-extensor. For muscles with 2-5 level of muscle strength, significant dissociation of fasciculation grade was common, especially among patients with slow rapid progression rate and both upper and lower motor neuron (UMN and LMN) involvement. As for non-ALS patients, no significant difference was observed in fasciculation intensity between antagonistic muscles. CONCLUSION: Split phenomenon of fasciculation between antagonistic muscles was common and relatively specific in ALS patients. Muscle strength, progression rate, and UMN involvement were influence factors of the split phenomenon of fasciculation intensity.

Incidence of amyotrophic lateral sclerosis-associated genetic variants: a clinic-based study.

OBJECTIVE: This study is to determine the incidence of genetic forms of amyotrophic lateral sclerosis (ALS) in clinic-based population. METHODS: Next-generation sequencing (NGS) of whole exome sequencing (WES) was conducted among a total of 374 patients with definite or probable ALS to identify ALS-associated genes based on ALSoD database ( https://alsod.ac.uk ) [2023-07-01]. RESULTS: Variants of ALS-associated genes were detected in 54.01% (202/374) ALS patients, among which 8.29% (31/374) were pathogenic/likely pathogenic (P/LP). The detection rates of P/LP variants were significantly higher in familial ALS than sporadic ALS (42.31% vs 5.75%, p < 0.001), while VUS mutations were more commonly detected in sporadic ALS (23.07% vs 47.13%, p = 0.018). There is no significant difference in detection rate between patients with and without early onset (8.93% vs 7.77%), rapid progression (9.30% vs 8.91%), cognitive decline (15.00% vs 7.93%), and cerebellar ataxia (20.00% vs 8.15%) (p > 0.05). CONCLUSION: Over half of our ALS patients carried variants of ALS-related genes, most of which were variants of uncertain significance (VUS). Family history of ALS could work as strong evidence for carrying P/LP variants regarding ALS. There was no additionally suggestive effect of indicators including early onset, progression rate, cognitive decline, or cerebellar ataxia on the recommendation of genetic testing in clinical practice.

Facial onset sensory and motor neuronopathy (FOSMN syndrome): Cases series and systematic review.

OBJECTIVE: To provide new and comprehensive evidence for diagnosis and management of FOSMN syndrome. METHODS: We reviewed our database to identify patients with FOSMN syndrome. Online database including PubMed, EMBASE, and OVID were also searched for relevant cases. RESULTS: We identified a total of 71 cases, including 4 cases from our database and 67 ones from online searching. A predominance of male was observed [44 (62.0%)] with median onset age of 53 (range: 7-75) years old. The median (range) disease duration was 60 (3-552) months at the time of the visit. The initial symptoms could be sensory deficits in face (80.3%) or oral cavity (4.2%), bulbar paralysis (7.0%), dysosmia (1.4%), dysgeusia (4.2%), weakness or numbness of upper limbs (5.6%), or lower limbs (1.4%). Abnormal blink reflex was presented in 64 (90.1%) patients. CSF tests showed elevated protein level in 5 (7.0%) patients. Six (8.5%) patients had MND-related gene mutation. Five (7.0%) patients showed transient responsiveness to immunosuppressive therapy, then deteriorated relentlessly. Fourteen (19.7%) patients died, with an average survival time of around 4 years. Among them, five patients died of respiratory insufficiency. CONCLUSION: The age of onset, progress of disease course, and prognosis of FOSMN syndrome could be varied significantly. The prerequisites of diagnosis were progressive and asymmetric lower motor neuron dysfunction, with sensory dysfunction which usually showed in face at the onset. Immunosuppressive therapy could be tried in some patients with suspected inflammatory clues. In general, FOSMN syndrome tended to be motor neuron disease with sensory involvement.

Evaluation of the coracoid bone tunnel placement on Dog Bone™ button fixation for acromioclavicular joint dislocation: a cadaver study combined with finite element analysis.

BACKGROUND: Dog Bone™ button fixation is frequently used to treat acromioclavicular joint (ACJ) dislocation. However, various studies have reported complications after fixation. OBJECTIVE: To investigate the effect of the coracoid bone tunnel location on the treatment of ACJ dislocation through single-tunnel coracoclavicular (CC) ligament fixation with the Dog Bone™ button. METHODS: Six cadaveric shoulders were used. Each specimen was subjected to five testing conditions in the following order: (1) normal ACJ (Gn); (2) acromioclavicular and CC ligaments were removed (G0); (3) CC ligament reconstruction was performed using the Dog Bone™ technique, and the coracoid bone tunnel was at the center of the coracoid base (G1); (4) reconstruction was performed at 5 mm distal from the G1 site, along the axis of the coracoid (G2); (5) reconstruction was performed at 10 mm distal from the G1 site, along the axis of the coracoid (G3). The angles of pronation and supination of the clavicle under the same load (30 N) were measured. Next, a finite element (FE) model was created using computed tomography (CT) images of the normal shoulder. Model 1 (M1), model 2 (M2), and model 3 (M3) correspond to G1, G2, and G3, respectively. A force of 70 N was applied as a vertical upward load to the distal clavicle. Subsequently, the von Mises stress, the strain LE along the FiberWire, and the displacement nephogram of the three models were obtained. RESULTS: After single-tunnel CC ligament fixation using the Dog Bone™ technique, the clavicle in the G2 group (20.50 (19.50, 21.25) °, 20.00 (18.75, 21.25) °) had the best rotational stability. The peak von Mises stress, the strain LE along the FiberWire, and the maximum displacement were smaller in M2 than in M1 and M3. CONCLUSIONS: When the coracoid bone tunnel was located 5 mm anterior to the center of the coracoid base (along the axis of the coracoid), the clavicle showed greater rotational stability.

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound.

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

Chronic inflammatory demyelinating polyradiculoneuropathy concomitant with nephropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of the most common autoimmune peripheral neuropathies in adults. Membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other nephropathy have been reported in CIDP patients and are possibly correlated to CIDP pathogenesis. This study reviewed the previously described cases of patients with CIDP and nephropathy in order to provide comprehensive evidence on the diagnosis and treatment regarding CIDP patients in the context of renal diseases. METHOD: We reviewed our database to identify patients with CIDP and nephropathy. Online database including PubMed, EMBASE, and OVID were searched for relevant cases. RESULTS: We identified a total of 18 cases with CIDP and nephropathy, including 2 cases from our database and 16 ones from online searching. A predominance of male was observed [14 (77.8%)] with the mean age of 53.3 (standard deviation, SD: 16.6) years old. Almost all patients complained paresthesia in distal limbs (94.4%), except one only presented weakness of four extremities. Corticosteroids were prescribed for 14 (77.8%) patients, and 10 showed responsiveness. Three patients experienced relapses during the gradual tapering of steroids. CONCLUSION: The same immune-mediated pathogenesis may be involved in CIDP and concomitant nephropathy. Male and sensory-predominant CIDP are red flags for complications of renal diseases in CIDP patients. Corticosteroids remain the first-line treatment for CIDP when complicated with renal diseases. Slower tapering or long-term maintenance of steroids may be beneficial for the prognosis of patients with CIDP and nephropathy.

Nerve ultrasound may help predicting response to immune treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUNDS: Nerve ultrasound has been proven to be an accurate tool in diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, its value in guiding treatment has not been well evaluated. The aim of this study was to explore whether nerve ultrasound and its changing trend could predict the response to immune treatment in CIDP. METHODS: Eighty-nine therapy-naive CIDP patients were recruited prospectively and treated with steroids and/or intravenous immunoglobulin (IVIG). Ultrasonographic and electrophysiological studies were performed on the median and ulnar nerves before treatment in all patients and followed up in 45 patients. The cross-sectional area (CSA) was measured at ten sites on both the median and ulnar nerves. RESULTS: The response rate to steroids (95%) was significantly higher than that to IVIG (70%) (P = 0.001) in patients with normal or moderately enlarged CSA, while there was no significant difference in the response rate between steroid therapy (84%) and IVIG (75%) (P = 0.653) in patients with markedly enlarged CSA. CSAs decreased in 15 patients during follow-up, most of whom had good IVIG and steroid responses (83%) and no need for immune suppressant treatment (82%). CONCLUSIONS: Nerve ultrasonography could help guide treatment strategies in patients with CIDP. Patients with normal or moderately enlarged CSA may respond better to steroids than to IVIG. The decrease in CSA after treatment may also indicate better prognosis.

Blood-brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia.

OBJECTIVE: We aim to investigate blood-brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD) and further determine the effect of these factors on the survival of ALS. METHODS: This was a retrospective study of 113 ALS patients, 12 ALS-FTD patients, and 40 disease controls hospitalized between September 2013 and October 2020. CSF parameters including total protein (TP), albumin (Alb), immunoglobulin-G (IgG), and MBP were collected and compared between groups. The CSF-TP, CSF-Alb, CSF-IgG, and CSF/serum quotients of Alb and IgG (QAlb, QIgG) were used to reflect the BBB status. Patients were followed up until December 2020. Cox regression and Kaplan-Meier method were used for survival analysis. RESULTS: The CSF-TP, CSF-Alb, and CSF-IgG concentrations were significantly higher in patients than controls (p < 0.01). Increased CSF-TP and CSF-IgG was found in 45 (39.8%) and 27 (23.9%) ALS patients, while in 7 (58.3%) and 5 (41.7%) ALS-FTD patients. The level of CSF-Alb, CSF-IgG, and CSF-MBP were significantly higher in patients with ALS-FTD than ALS. MBP showed a moderate accuracy in the distinction between ALS-FTD and ALS (AUC = 0.715 ± 0.101). No difference in MBP was found between patients and controls. Kaplan-Meier analysis indicated that a higher CSF-TP, CSF-IgG, QIgG, or QAlb was significantly associated with shorter survival. Cox regression model showed that CSF-TP, CSF-IgG, and QIgG were independent predictors of survival. CONCLUSION: Our findings suggested that BBB dysfunction was more prominent in ALS-FTD than ALS and associated with a worse prognosis. Further studies are needed to determine the role of CSF-MBP as a biomarker in ALS.

Nerve ultrasound studies in POEMS syndrome.

INTRODUCTION: The aim of our study was to assess the ultrasonographic features of peripheral nerves in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. METHOD: 34 POEMS syndrome patients and 26 healthy control (HC) participants were recruited prospectively. Cross-sectional area (CSA) was measured in nerves of limbs, trunks of brachial plexus, and cervical nerve roots RESULTS: The CSAs were mildly enlarged at the arm segment of median nerve, elbow segment of ulnar nerve and upper trunk, moderately enlarged at the forearm segment of both median and ulnar nerve, upper trunk of brachial plexus, and C6, C7 cervical nerve roots, and markedly enlarged at the arm segment of ulnar nerve, middle and lower trunk of brachial plexus, as well as C5 cervical root. DISCUSSION: The CSAs of upper limb nerves were larger in POEMS syndrome patients than in HCs, and the enlargements were most prominent proximally.

Fasciculation differences between ALS and non-ALS patients: an ultrasound study.

BACKGROUND: Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. METHODS: Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. RESULTS: The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0-3) in ALS and 0 (0-0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. DISCUSSION: The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. CONCLUSIONS: The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Cross-sectional area reference values for sonography of nerves in the upper extremities.

INTRODUCTION: Detailed morphological features of the peripheral nerves could improve the diagnostic sensitivity in some polyneuropathies. In this study we aimed to establish multiple-site, cross-sectional area (CSA) reference values for peripheral nerves of upper extremities in a healthy Chinese population. METHODS: One hundred eleven healthy subjects, 15 to 70 years of age, were prospectively recruited. CSA at predetermined sites of the median, ulnar, radial nerves, and brachial plexus was measured bilaterally. Ten consecutive sites were studied along the median/ulnar nerves. RESULTS: The CSA at ten sites of the median nerve ranged from 5.59 ± 0.89 to 8.43 ± 1.30 mm2 , and for the ulnar nerve from 2.94 ± 0.57 to 5.63 ± 1.08 mm2 . Both age and gender correlated with nerve CSA at most sites. DISCUSSION: CSA was not uniform along the length of the median and ulnar nerves. The multiple-site reference values could be helpful for investigating polyneuropathies in the Asian population.

Abduction range: A potential parameter for the long exercise test in hypokalemic periodic paralysis during inter-attack periods.

BACKGROUND: The abduction range of the little finger in the long exercise test (ET) has rarely been reported in patients with hypokalemic periodic paralysis (HypoPP) during inter-attack periods, and the diagnostic value requires clarification. METHODS: The long ET was performed in 43 HypoPP patients during inter-attack periods and in 20 healthy controls (HCs). The compound muscle action potential (CMAP) and the abduction range of the little finger were recorded concurrently. RESULTS: There were significant differences in the percent changes of the CMAP amplitudes and the abduction ranges after exercise between HypoPP patients and the HCs. The curve of percent changes in abduction ranges overlapped substantially with that of the CMAP amplitudes, and the sensitivity, specificity, and cutoff values were 0.860, 0.900, and 22.6%, respectively. CONCLUSIONS: The abduction range of the little finger can serve as a novel parameter in the long ET for the diagnosis of HypoPP during inter-attack periods.

Internalization of the TAT-PBX1 fusion protein significantly enhances the proliferation of human hair follicle-derived mesenchymal stem cells and delays their senescence.

OBJECTIVES: To express a TAT-PBX1 fusion protein using a prokaryotic expression system and to explore potential effects of TAT-PBX1 in the proliferation and senescence of human hair follicle-derived mesenchymal stem cells. RESULTS: The TAT-PBX1 fusion was produced in inclusion bodies and heterogenously expressed in Rosetta (DE3) cells. Immunofluorescence staining showed that TAT-PBX1 fusion proteins were internalized by human hair follicle-derived mesenchymal stem cells. The growth rate of cells was increased after treatment with more than 5.0 µg/mL of TAT-PBX1. The rate of senescence-associated ß-galactosidase positive cells was reduced in the 10.0 µg/mL TAT-PBX1 group (28%) than the 0 µg/mL control group (60%). Cells treated with the TAT-PBX1 fusion protein showed higher expression of p-AKT (1.22-fold that of the control), which indicates that TAT-PBX1 activated AKT pathway after cellular uptake. CONCLUSIONS: The TAT-PBX1 fusion protein increased the proliferation of hair follicle mesenchymal stem cells and delayed their senescence by activating the AKT pathway following internalization by cells.

Enrichment of superoxide dismutase 2 in glioblastoma confers to acquisition of temozolomide resistance that is associated with tumor-initiating cell subsets.

BACKGROUND: Intratumor subsets with tumor-initiating features in glioblastoma are likely to survive treatment. Our goal is to identify the key factor in the process by which cells develop temozolomide (TMZ) resistance. METHODS: Resistant cell lines derived from U87MG and A172 were established through long-term co-incubation of TMZ. Primary tumors obtained from patients were maintained as patient-derived xenograft for studies of tumor-initating cell (TIC) features. The cell manifestations were assessed in the gene modulated cells for relevance to drug resistance. RESULTS: Among the mitochondria-related genes in the gene expression databases, superoxide dismutase 2 (SOD2) was a significant factor in resistance and patient survival. SOD2 in the resistant cells functionally determined the cell fate by limiting TMZ-stimulated superoxide reaction and cleavage of caspase-3. Genetic inhibition of the protein led to retrieval of drug effect in mouse study. SOD2 was also associated with the TIC features, which enriched in the resistant cells. The CD133+ specific subsets in the resistant cells exhibited superior superoxide regulation and the SOD2-related caspase-3 reaction. Experiments applying SOD2 modulation showed a positive correlation between the TIC features and the protein expression. Finally, co-treatment with TMZ and the SOD inhibitor sodium diethyldithiocarbamate trihydrate in xenograft mouse models with the TMZ-resistant primary tumor resulted in lower tumor proliferation, longer survival, and less CD133, Bmi-1, and SOD2 expression. CONCLUSION: SOD2 plays crucial roles in the tumor-initiating features that are related to TMZ resistance. Inhibition of the protein is a potential therapeutic strategy that can be used to enhance the effects of chemotherapy.

Serial nerve ultrasound and motor nerve conduction studies in chronic inflammatory demyelinating polyradiculoneuropathy.

INTRODUCTION: The objective of this study was to evaluate the correlation between cross-sectional area (CSA) and nerve conduction studies (NCS) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to determine how CSA changes over time after standard treatment. METHODS: Fifty-four patients with CIDP were recruited prospectively, and 21 patients were followed for more than 6 months. Ultrasonography and motor NCS were performed in the median and ulnar nerves. RESULTS: No or weak correlation was observed between the maximum CSA and motor conduction velocity. There were segmental nerve enlargements at 61% of sites with conduction block or temporal dispersion. Among 19 patients with clinical improvement after immunotherapy, CSA decreased to normal in 5, increased in 10, and were unchanged in 4. DISCUSSION: Different patterns of CSA and motor NCS changes after immune treatment may indicate different CIDP pathologic mechanisms. Exploration of these pathologic mechanisms could guide treatment choices in the future. Muscle Nerve, 2019.

Excessive daytime sleepiness in Chinese patients with sporadic amyotrophic lateral sclerosis and its association with cognitive and behavioural impairments.

OBJECTIVE: To examine the frequency and clinical features of excessive daytime sleepiness (EDS) and its association with cognitive and behavioural impairments in patients with amyotrophic lateral sclerosis (ALS). METHODS: We conducted a cross-sectional investigation to explore the frequency and clinical features of EDS in a group of 121 Chinese patients with ALS compared with 121 age-matched and sex-matched healthy subjects. EDS was diagnosed using the Epworth Sleepiness Scale (ESS). Other characteristics of patients with ALS including sleep quality, REM sleep behaviour disorder (RBD), restless legs syndrome (RLS), cognition, behaviour, depression and anxiety were also evaluated. RESULTS: EDS was significantly more frequent in patients with ALS than in controls (26.4% vs 8.3%; p<0.05). Patients with ALS with EDS scored lower scores on the revised ALS Functional Rating Scale (ALSFRS-R), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and MMSE and MoCA delayed memory subitems and higher on the Frontal Behavioural Inventory (FBI) than patients with ALS without EDS. ESS scores correlated with global ALSFRS-R, FBI, MMSE and MoCA scores and MMSE and MoCA delayed memory scores. RLS and global ALSFRS-R scores were independently associated with EDS in patients with ALS. CONCLUSIONS: We identified a high frequency of EDS symptoms in Chinese patients with ALS, and these patients might have more serious physical, cognitive and frontal behaviour impairment. Patients with ALS might improve quality of life from the timely recognition and optimised management of EDS symptoms. Our results further suggest that ALS is a heterogeneous disease that might exhibit abnormal sleep-wake patterns.

Single-fiber EMG with concentric electrodes in lambert-eaton myasthenia.

INTRODUCTION: We analyzed jitter recordings made with concentric needle electrode (CNE) single-fiber electromyography (SFEMG) in Lambert-Eaton myasthenia (LEM). METHODS: Fifteen subjects diagnosed with LEM were studied using CNE-SFEMG in the extensor digitorum (ED) and tibialis anterior (TA) muscles. CNE-SFEMG in the ED and TA was also used to evaluate 12 and 10 healthy controls (HCs), respectively. RESULTS: Ten men and 5 women were diagnosed with LEM based on an increase of 100% in compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation. All patients exhibited markedly greater jitter in the ED (88.8 ± 23.2 µs) and TA (92.2 ± 30.2 µs) than HCs (28.3 ± 3.4 µs and 30.9 ± 5.1 µs, respectively). CONCLUSIONS: CNE-SFEMG is sensitive for discovering abnormalities in neuromuscular transmission in LEM. Muscle Nerve 56: 253-257, 2017.

A Chinese female Morvan patient with LGI1 and CASPR2 antibodies: a case report.

BACKGROUND: Morvan syndrome is a rare disorder characterized by the combination of peripheral nerve hyperexcitability, encephalopathy and dysautonomia with marked insomnia. It was reported to have association to antibodies to voltage-gated potassium channels including contactin associated protein-like 2 antibodies (CASPR2-Ab) and leucine-rich glioma inactivated protein 1 antibodies (LGI1-Ab). LGI1-Ab was reported to associate with seizures, amnesia, confusion, hyponatraemia and a good prognosis, while CASPR2-Ab with peripheral presentations, probable risk for tumor and a poor prognosis. The vast majority of Morvan syndrome patients were male, with normal magnetic resonance imaging of the brain. CASE PRESENTATION: We report a female case presenting with a combination of bilateral leg pain, widespread myokymia, memory disturbance, seizure, hyperhidrosis and insomnia. She had antibodies targeting CASPR2 and LGI1, tested by the indirect immunofluorescence test, which demonstrated the diagnosis of typical Morvan syndrome as well as classical limbic encephalitis. Cranial MRI revealed bilateral hyper-intensity of the medial temporal lobe, insular lobe and basal ganglia on T2/FLAIR and DWI sequence. As the treatment carried on, her serum LGI1-Ab disappeared and her memory loss, seizure and confusion quickly relieved. But her peripheral presentations did not relieve until serum CASPR2-Ab turned negative. Intravenous immunoglobulin treatment showed limited efficacy while she achieved almost complete remission with corticosteroids therapy. CONCLUSIONS: This case provides a rare female resource of Morvan syndrome, which is the first patient with both CASPR2-Ab and LGI1-Ab positive Morvan syndrome in China and one of the few female patients with Morvan syndrome reported so far. Through the detailed analysis of her clinical course, the diverse and overlapping clinical phenotype of CASPR2-Ab and LGI1-Ab in patients with Morvan syndrome was obvious and interesting.