Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN. METHODS: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed. RESULTS: A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p < .05) in distinguishing T2DM with DSPN from those without (AUC = 0.720). CONCLUSIONS: In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted.

Establishment of a new classification system for chronic inflammatory demyelinating polyneuropathy based on unsupervised machine learning.

INTRODUCTION/AIMS: A model for predicting responsiveness to immunotherapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) has not been well established. We aimed to establish a new classifier for CIDP patients based on clinical characteristics, laboratory findings, and electrophysiological features. METHODS: The clinical, laboratory, and electrophysiological features of 172 treatment-naïve patients with CIDP between 2003 and 2019 were analyzed using an unsupervised hierarchical clustering. The identified pivotal features were used to establish simple classifications using a tree-based model. RESULTS: Three clusters were identified: 1, n = 65; 2, n = 70; and 3, n = 37. Patients in Cluster 1 scored lower on the disability assessment score before treatment. More patients in Clusters 2 (90.0%) fulfilled demyelinating criteria than patients in Cluster 1 (30.8%, p < .001). Cluster 3 had more patients with chronic kidney disease (CKD) (27.0%) and hypoalbuminemia (3.40 g/dL) than did Cluster 2 (CKD: 0%, p < .001; hypoalbuminemia: 4.09 g/dL, p < .001). The responsiveness to pulse steroid therapy was higher in Cluster 2 (70.0%) than in Clusters 1 (31.8%; p = .043) and 3 (25.0%; p = .014). A tree-based model with four pivotal features classified patients in our cohort into new clusters with high accuracy (89.5%). DISCUSSION: The established hierarchical clustering with the tree-based model identified key features contributing to differences in disease severity and response to pulse steroid therapy. This classification system could assist clinicians in the selection of treatments and could also help researchers by clustering patients for clinical treatment trials.

The correlation of small fiber neuropathy with pain intensity and age in patients with Fabry's disease: A cross sectional study within a large Taiwanese family.

BACKGROUND: The relationships among small fiber neuropathy, age, sex and pain intensity in the context of Fabry's disease remain unclear. We aim to study the correlations of small fiber neuropathy, age, sex and pain intensity in Fabry patients. METHODS: We evaluated C-fiber function by recording the withdrawal latencies to painful heat stimulus (WLPHS) when each subject's right hand was immersed in a 50 °C hot water bath and correlated this parameter with the patient's perceived pain intensity and quality of life assessed by the short-form McGill Pain Questionnaire (SF-MPQ) in a large Taiwanese Fabry family and normal controls. RESULTS: Male Fabry patients showed a significantly increased WLPHS compared to that of normal controls. Furthermore, male Fabry patients showed a positive correlation of increased WLPHS with patient age. The SF-MPQ of male Fabry patients showed a bell distribution with age, and maximal pain scores were detected between the ages of the early 20s and late 40s. In contrast, the female Fabry patients had variable associations of WLPHS and SF-MPQ with age. CONCLUSIONS: We proposed a probable mechanism by which globotriaosylceramide (Gb3) or globotriaosylsphingosine (lyso-Gb3) is gradually deposited into the small nerve bundles with increasing age, which induces continuous damage and produces injury discharges to sustain neuropathic pain in young male Fabry patients. However, once the small fibers are reduced to a certain degree, they no longer produce enough noxious discharges to sustain neuropathic pains in older male Fabry patients, which leads these patients to have lower SF-MPQ scores. In contrast, female Fabry patients had less and variable small fiber damage, pain intensity and clinical signs/symptoms.

Isaacs' syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report.

BACKGROUND: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. CASE PRESENTATION: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. CONCLUSIONS: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma.

The First Guillain-Barr? Syndrome After SARS-CoV-2 Vaccination in Taiwan.

PURPOSE: Guillain-Barre syndrome (GBS) is an immune-mediated disease of the peripheral nerves and could be fatal and has severe neurologic complications. This study herein reports the clinical course of the first patient of GBS after SARS-CoV-2 Oxford/AstraZeneca vaccination in Taiwan. CASE REPORT: A 38-year-old woman who presented with progressive numbness and weakness of both upper and lower limbs over 1 week. Ascending patterns was noted, and bilateral leg were more severe with diffused absence of deep tendon reflex. Clinical examination and investigation findings confirmed with the diagnosis of GBS. Deterioration of muscle power and respiratory failure had developed during the hospitalization. She had no common GBS predisposing history, but she had received her first SARS-CoV-2 Oxford/AstraZeneca vaccination intramuscularly 10 days prior to her symptoms. Clinical symptoms had much improved after double filtration plasmapheresis. CONCLUSION: Our case is the first case of GBS developed after AstraZeneca vaccine injection in Taiwan, presenting with atypical manifestation of early facial and bulbar involvement. The vaccination associated GBS should be closely monitored as other safety profile, since it may result in respiratory failure and severe neurologic complications. Keyword: Guillain-Barre Syndrome, SARS-CoV-2 Vaccination.

Altered Metabolic Profiles of the Plasma of Patients with Amyotrophic Lateral Sclerosis.

Currently, there is no objective biomarker to indicate disease progression and monitor therapeutic effects for amyotrophic lateral sclerosis (ALS). This study aimed to identify plasma biomarkers for ALS using a targeted metabolomics approach. Plasma levels of 185 metabolites in 36 ALS patients and 36 age- and sex-matched normal controls (NCs) were quantified using an assay combining liquid chromatography with tandem mass spectrometry and direct flow injection. Identified candidates were correlated with the scores of the revised ALS Functional Rating Scale (ALSFRS-r). Support vector machine (SVM) learning applied to selected metabolites was used to differentiate ALS and NC subjects. Forty-four metabolites differed significantly between ALS and NC subjects. Significant correlations with ALSFRS-r score were seen in 23 metabolites. Six of them showing potential to distinguish ALS from NC-asymmetric dimethylarginine (area under the curve (AUC): 0.829), creatinine (AUC: 0.803), methionine (AUC: 0.767), PC-acyl-alkyl C34:2 (AUC: 0.808), C34:2 (AUC: 0.763), and PC-acyl-acyl C42:2 (AUC: 0.751)-were selected for machine learning. The SVM algorithm using selected metabolites achieved good performance, with an AUC of 0.945. In conclusion, our findings indicate that a panel of metabolites were correlated with disease severity of ALS, which could be potential biomarkers for monitoring ALS progression and therapeutic effects.

Cross-Sectional Area Reference Values for Sonography of Peripheral Nerves in Taiwanese Adults.

Background: Neuromuscular ultrasound is a complementary technology that aids in the diagnosis of peripheral neuropathy. The interpretation of neuromuscular ultrasound results requires the use of accurate normative cross-sectional area (CSA) reference values. This study aims to provide CSA reference values specific to Taiwanese adults for Sonography of peripheral nerves in the upper and lower extremities. Methods: The study cohort included 66 healthy subjects (36 women; 30 men). A linear probe was used to measure the CSA of the median, ulnar, radial, tibial, sural, and peroneal nerves at multiple sites. These data were analyzed to determine standard ranges for the CSA at each site (reference range = mean ± 2 × SD) and identify correlations between the CSA and patient characteristics. Results: Normative CSA ranges were determined for all the assessed nerve sites, revealing that the nerve sizes in this Taiwanese population were smaller than Caucasian populations but comparable to those reported for other Asian cohorts. Men tended to have larger nerves than women, even after adjusting for height and weight. The size of ulnar nerve in the cubital tunnel and the peroneal nerve in the popliteal fossa correlated negatively with increasing age. The nerve size correlated positively with increasing weight and BMI at several sites, correlation of median nerve in the forearm with weight and BMI was significant after multiple testing. Significant correlation was also found between size of ulnar nerve in cubital tunnel and decreasing height. Conclusion: We provide reference ranges for neuromuscular ultrasound CSA values for the upper and lower extremities that are specific to the Taiwanese population. These reference values may be useful for evaluating peripheral neuropathy in Taiwanese subjects.

Reappraisal of the incidence, various types and risk factors of malignancies in patients with dermatomyositis and polymyositis in Taiwan.

Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40-59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.

Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan.

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder.

OBJECTIVES: Blood-brain barrier (BBB) disruption is a critical pathological process involved in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterized the profile of five cell adhesion molecules in patients with NMOSD. METHODS: We measured levels of cell adhesion molecules, including ICAM-1, ICAM-2, VCAM-1, PECAM-1, and NCAM-1, in the serum of 28 patients with NMOSD, 24 patients with multiple sclerosis (MS), and 25 healthy controls (HCs). RESULTS: ICAM-2 levels (median: 394.8 ng/mL) were increased in patients with NMOSD compared with MS (267.1 ng/mL, P = 0.005) and HCs (257.4 ng/mL, P = 0.007), and VCAM-1 and ICAM-1 levels were higher in patients with NMOSD (641.9 ng/mL and 212.7 ng/mL, respectively) compared with HCs (465 ng/mL [P = 0.013] and 141.8 ng/mL [P = 0.002], respectively). However, serum PECAM-1 levels were lower in patients with NMOSD (89.62 ng/mL) compared with MS (106.9 ng/mL, P = 0.015) and HCs (107.2 ng/mL, P = 0.007). Receiver operating characteristic curve analysis revealed that PECAM-1 (area under the curve (AUC): 0.729) and ICAM-2 (AUC: 0.747) had adequate abilities to distinguish NMOSD from MS, and VCAM-1 (AUC: 0.719), PECAM-1 (area under the curve: 0.743), ICAM-1 (AUC: 0.778), and ICAM-2 (AUC: 0.749) exhibited potential to differentiate NMOSD and HCs. Serum levels of PECAM-1 also demonstrated a negative correlation with Kurtzke Expanded Disability Status Scale scores in patients with NMOSD. INTERPRETATION: Our results reveal possible BBB breakdown signals specifically observed in NMOSD and highlight the potential role of cell adhesion molecules as biomarkers of this disease.

Diabetic Distal Symmetrical Polyneuropathy: Correlation of Clinical, Laboratory, and Electrophysiologic Studies in Patients with Type 2 Diabetes Mellitus.

This cross-sectional study is aimed at determining the prevalence of distal symmetrical polyneuropathy (DSPN) and diabetic peripheral neuropathic pain (DPNP) in participants with type 2 diabetes mellitus (T2DM); finding the risk factors for DSPN and DPNP via biochemical tests; and correlating DSPN and DPNP with the results of electrophysiologic studies, quantitative sensory tests, and neurologic examination. The 145 participants with T2DM enrolled were divided into the DSPN (abnormal nerve conduction studies (NCS) with signs of polyneuropathy), subclinical DSPN (abnormal NCS without signs of polyneuropathy), minimal DSPN (normal NCS with signs of polyneuropathy), and no DSPN groups. The biochemical risk factors of diabetic peripheral neuropathy were investigated. Neurologic examinations, laboratory tests, NCS, vibration threshold tests, and thermal threshold tests were conducted. The modified Michigan Neuropathy Screening Instrument (mMNSI) and Douleur Neuropathique 4 were used to evaluate the severity of DSPN and DPNP, respectively. In all, 30% of participants had DSPN and 11% had DPNP. DSPN correlated strongly with male gender and higher glycohaemoglobin levels; NCS abnormality correlated with higher glycohaemoglobin levels; DSPN severity correlated with NCS of each stimulating nerve. DPNP commonly occurred with clinical and electrophysiologic evidence of DSPN. Symptomatic diabetic polyneuropathy significantly correlated with longer disease duration, higher glycohaemoglobin levels, and abnormal vibration tests. The thermal threshold test combined with nerve conduction tests could detect most of the patients with DSPN, subclinical DSPN, and minimal DSPN. Poor diabetic control was independently associated with the development of DSPN. DPNP was associated with DSPN. The combination of thermal threshold tests with NCS can potentially provide the diagnosis of DSPN.

Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia.

Our previous animal studies and several human clinical trials have shown that granulocyte-colony stimulating factor (GCSF) can attenuate neuropathic pain through various mechanisms. GCSF itself is also a multipotent cytokine that can modulate microribonucleic acid (microRNA) expression profiles in vitro. In this study, we used the NanoString nCounter analysis system to screen the expression of different rodent microRNAs at early stage after nerve injury and studied the expression of related cytokines/chemokines in the dorsal root ganglia (DRGs) of rats that underwent chronic constriction injury (CCI) to explore the underlying mechanisms of the analgesic effects of GCSF. We found that microRNA-122 expression was downregulated by CCI; in contrast, GCSF treatment significantly upregulated microRNA-122 expression in the DRGs of CCI rats on the 1st day after nerve injury. We further studied the expression of different cytokines/chemokines (IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1)) that were modulated by microRNA-122. MCP-1 has been reported to participate in neuropathic pain development, and its expression on the DRGs of vehicle-treated CCI rats was significantly higher than that on the DRGs of sham-operated rats; in contrast, GCSF-treated rats exhibited significantly lower MCP-1 expression in the DRG than vehicle-treated rats on the 7th day after nerve injury. An early GCSF treatment can suppress MCP-1 expressions, through upregulating microRNA-122 expressions in the DRGs of CCI rats at an earlier stage, thus indirectly attenuating neuropathic pain development.

The etiologies and prognosis associated with spinal cord infarction.

BACKGROUND: This study aims to investigate the etiology and prognosis of spinal cord infarction (SCI). METHODS: Over a period of 16 years, we retrospectively analyzed 31 patients with SCI. Demographic features and symptom presentations were carefully documented. Etiology-specific MRI features, such as the length and distribution of the lesions and owl's eyes sign, were recorded and analyzed to determine their associations with the clinical signs/symptoms. RESULTS: In total, seven patients had aortic or vertebral artery dissections. We divided the patients with SCI into two groups: those with or without vessel dissection. Among SCI patients, the onset age was younger, and the proportion of patients with long-segment lesions and posterior pattern involvement on axial view was higher in the group with dissection than in the group without dissection (all P < 0.05). The lesions were frequently located in the upper cervical or lower thoracic-lumbar regions, and the lengths of the lesions were associated with 1-month outcomes, suggesting that artery dissection may contribute to the longitudinal and posterior extension of SCI. In contrast, among patients without dissection, the range of longitudinal extensions of in spans of vertebral bodies was broader (range, 1-8). A higher proportion of patients had focal pain adjacent to the lesion (P = 0.05) and a poorer 1-month outcome (P = 0.04) in the long-segment lesion group than in the short-segment lesion group. CONCLUSIONS: A detailed history and the use of modern imaging tools may help clinicians search for vessel dissection and other etiologies, evaluate the spatial extension of lesions in SCI, and predict prognosis.

Gulllain-Barre Syndrome After Trivalent Influenza Vaccination in Adults.

Lines of evidence suggest trivalent influenza vaccination may be associated with Guillain-Barre syndrome (GBS), an immune-mediated acute inflammatory neuropathy. On the other hand, this vaccination protects against influenza infection, which has been demonstrated as a trigger of GBS. To clarify the net effect of trivalent influenza vaccines on GBS, we conducted a retrospective nationwide nested case-control study using the database of the Taiwan National Health Insurance program. We identified 182 hospitalized patients with GBS aged ≥50 years from 2007 to 2015 as the cases, and 910 hospitalized patients, matched by gender, age, date of hospitalization, comorbidities, and medications, as the control subjects. Nearby and remote exposures of vaccination were defined as subjects who had received trivalent influenza vaccine 42 (nearby exposure) and 90 days (remote exposure) before the date of hospitalization, respectively. We found 7 (3.85%) GBS patients and 26 (2.86%) matched control subjects who demonstrated nearby exposures of influenza vaccine (odds ratio: 1.46, 95% confidence interval: 0.56-3.78). Seventeen (9.34%) GBS patients were exposed to influenza vaccines remotely, while the number of remote exposure of influenza vaccines in matched control subjects was 72 (7.91%, odds ratio: 1.26, 95% confidence interval: 0.67-2.38). These results do not support an association between trivalent influenza vaccine and GBS among the patients aged ≥50 years.

A prospective, observational study on conversion of clinically isolated syndrome to multiple sclerosis during 4-year period (MS NEO study) in Taiwan.

IMPORTANCE: CIS to MS conversion rates vary depending on population cohorts, initial manifestations, and durations of follow-up. OBJECTIVE: To investigate conversion rate of patients from CIS to MS and the prognostic significance of demographic and clinical variables in Taiwanese population. DESIGN: Nationwide, prospective, multi-centric, observational study from November 2008 to November 2014 with 4 years follow-up. SETTING: Multi-centre setting at 5 institutions in Taiwan. PARTICIPANTS: 152 patients having single clinical event potentially suggestive of MS in last 2 years were enrolled as consecutive sample. 33 patients were lost to follow-up and 16 patients did not complete the study.103 patients completed the study. INTERVENTION(S) (FOR CLINICAL TRIALS) OR EXPOSURE(S) (FOR OBSERVATIONAL STUDIES): Natural progression from first episode of CIS to MS or NMO was observed. MAIN OUTCOME(S) AND MEASURE(S): Variables analysed were 'proportion of patients converting to MS or NMO after first episode of CIS', 'duration between first episode of neurological event and diagnosis of MS', 'status of anti-AQP4 IgG' and 'length of longest contiguous spinal cord lesion in MS patients'. Association between baseline characteristics and progression to MS from CIS was analyzed using multiple logistic regression. Multivariate time dependent effect of baseline characteristics on progression to MS was plotted. RESULTS: 14.5% patients with CIS converted to MS after 1.1 ± 1.0 years with greater predisposition (18.8%) in those having syndromes referable to the cerebral hemispheres. Conversion rate from ON to MS was 9.7%. 90.9% patients had mild disease course. 46.7% patients had abnormal MRIs at baseline, with 0.6±0.5 contrast enhanced lesions. 'Below normal BMI' and 'MRI lesion load (≥ 4 lesions)' were identified as risk indicators for the development of MS. Amongst the patients who developed NMO as diagnosed by modern criteria, 80% were positive for anti-AQP4 IgG antibody. CONCLUSIONS AND RELEVANCE: 'Below normal BMI' and 'number of demyelinating lesions (≥4)' are significant predictors of conversion from CIS to MS. A low conversion rate to MS in Taiwanese CIS patients and majority of them having a mild course and minimal disability suggest the roles of geographic, genetic and ethnic factors. TRIAL REGISTRATION: Non-trial observational study.

A comparison between spinal cord infarction and neuromyelitis optica spectrum disorders: Clinical and MRI studies.

This study aims to investigate the clinical features and magnetic resonance imaging (MRI) findings in patients with spinal cord infarction (SCI) and neuromyelitis optica spectrum disorders (NMOSDs). Over a period of 16 years, we retrospectively analyzed 39 patients with SCI and 21 patients with NMOSD. The demographic features and clinical presentations of both diseases were carefully documented. Etiology-specific MRI features, such as the length and distribution of the lesions, the owl's eyes sign and bright spotty lesions, were recorded and analyzed regarding their association with the clinical signs/symptoms. Patients with SCI were older than patients with NMOSD and had sudden onset of clinical symptoms with focal pain adjacent to the lesions. Concomitant spinal cord and vertebral body infarctions were frequently associated with aortic pathology (p = 0.04). In addition, artery dissection was highly associated with combined ASA and unilateral PSA infarctions and long segments of SCI (all p < 0.05). In contrast, patients with NMOSD had a relatively younger age of onset, female predominance and subacute progression of limbs weakness. As observed by MRI, the length and location of the lesions demonstrated significant differences between the two diseases (P < 0.01). The owl's eyes sign showed more frequently in patients with SCI than NMOSD (p < 0.01). The predicted prognoses in SCI and NMOSD were significantly associated with initial motor function (muscle power), after adjustments for age and gender (p < 0.01 and p = 0.02, respectively). Along with patient demographic characteristics, lesion features on MRI can help clinicians differentiate acute noncompressive myelopathy due to SCI from that due to NMOSD, which may lead to immediate initiation of adequate therapeutic measures.

Elevated serum levels of endothelin-1 in patients with chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, or non-hereditary, chronic demyelinating neuropathy. Currently, there is no reliable molecular biomarker that can identify CIDP patients as well as monitor disease severity. MATERIAL AND METHODS: We measured serum levels of endothelin-1 (ET-1), a factors involved in vasoconstrictive, inflammatory and nerve regenerative processes, in 20 CIDP, 21 acute inflammatory demyelinating polyneuropathy (AIDP), 37 multiple sclerosis (MS), and 10 Alzheimer's disease (AD) patients, as well as 26 healthy control (HC) subjects. RESULTS: Patients with CIDP demonstrated higher serum levels of ET-1 (2.07±1.07pg/mL) than those with AIDP (0.75±0.62ng/mL, P<0.001), AD (0.78±0.49pg/mL, P<0.001), as well as HCs (1.16±0.63pg/mL, P=0.002), while levels of ET-1 in patients with MS (2.10±0.81pg/mL) and CIDP were similar. Furthermore, the serum ET-1 levels significantly correlated with Inflammatory Neuropathy Cause And Treatment (INCAT) disability scale in CIDP patients. Receiver operating characteristic (ROC) curve showed good discrimination ability for ET-1 to distinguish CIDP patients from AIDP (AUC=0.883) or HCs (AUC=0.763). CONCLUSION: This study discloses the potential of serum ET-1 as a biomarker for CIDP.

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese.

BACKGROUND: The disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical. METHODS: We retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center. RESULTS: Eight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%). CONCLUSIONS: This study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.

Disturbance of Plasma Lipid Metabolic Profile in Guillain-Barre Syndrome.

Guillain-Barre Syndrome (GBS) is an inflammatory disease of the peripheral nervous system. Given that plasma metabolic profiles in GBS patients have never been explored, plasma samples of 38 GBS patients, 22 multiple sclerosis (MS) patients, and 40 healthy controls were analyzed by using untargeted and targeted metabolomics analysis. The untargeted analysis showed that levels of a set of plasma lipid metabolites were significantly decreased in GBS patients compared to the controls. Furthermore, the targeted analysis demonstrated that levels of 41 metabolites in GBS patients were significantly changed compared to either the controls or MS patients. A further metabolic analysis showed that 12 of 41 metabolites were significantly lower in classical GBS patients compared to Miller-Fisher syndrome. Among them, each of PCae C34:0, PCae C42:2, PCae C42:3, and SM C24:0 was inversely correlated with Hughes functional grading scale of GBS patients at both nadir and discharge. Receiver operating characteristic curve analysis of combination of three metabolites (PCaa C42:2, PCae C36:0 and SM C24:0) showed a good discrimination between the GBS and the controls (area under curve = 0.86). This study has demonstrated disruption of lipid metabolites in GBS may be potential biomarkers to indicate disease severity and prognosis of GBS.

Clinical and electrodiagnostic characteristics of nitrous oxide-induced neuropathy in Taiwan.

OBJECTIVE: Nitrous oxide-induced neuropathy is toxic neuropathy occasionally encountered in Taiwanese neurological clinics. Only several case reports described their electrodiagnostic features. We used a case-control design to investigate the detailed electrodiagnostic characteristics and possible factors relating to severe nerve injury. METHODS: We retrospectively reviewed 33 patients with nitrous oxide-induced neuropathy over a 10-year period and reported their demographic data, spinal cord MRI, laboratory examinations and nerve conduction studies. 56 healthy controls' nerve conduction studies were collected for comparison analysis. RESULTS: We noted significant motor and sensory amplitudes reduction, conduction velocities slowing, and latencies prolongation in most tested nerves compared to the controls. Similar nerve conduction study characteristics with prominent lower limbs' motor and sensory amplitudes reduction was observed in patient groups with or without abnormal vitamin B12 and/or homocysteine levels. Among those with lower limbs' motor or sensory amplitudes reduction <20% of the lower limit of normal, higher homocysteine levels were detected. CONCLUSIONS: Severe impairments of the lower limbs' sensory and motor amplitudes were frequently noted in patients with nitrous oxide exposure. Nitrous oxide exposure itself is an important factor for the development of neuropathy. SIGNIFICANCE: Our study contributes to the understanding of electrodiagnostic features underlying the nitrous oxide-induced neuropathy.