Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to ascertain the clinical manifestations of granulomatosis with polyangiitis (Wegener's) (GPA) with the involvement of the peripheral nervous system (PNS) and central nervous system (CNS). Summary: All neurologic inpatients in a hospital over a 12-year period were reviewed. Nine patients met both the ACR 1990 traditional format criteria for the classification of GPA and the Chapel Hill nomenclature mandatory criteria for GPA. We focused on the clinical presentation, serological data, biopsy reports, disease activities [as assessed by the Birmingham Vasculitis Activity Score (BVAS)], electrophysiology, and brain images. Nine patients met the diagnostic criteria for GPA. The neurological signs of the initial manifestation of GPA were found in 6/9 (67%) patients. Eight patients had GPA-related CNS involvement, including four patients with chronic hypertrophic pachymeningitis, with either diffuse or focal thickening; three had intracranial hemorrhages and two had orbital mass lesions with optic nerve compression. In addition, six patients showed PNS involvement, including three with asymmetric sensorimotor polyneuropathy, two with symmetric sensorimotor polyneuropathy, and one with bilateral mononeuropathy. Key Messages: Neurological manifestation is not uncommon and can be the first clinical sign of GPA. The involvement of both CNS and PNS raises the possibility of GPA in hospitalized neurologic patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: A case series of acute intermittent porphyria (AIP) is described that focuses on the clinical course of the disease with regard to neurological manifestations of the peripheral nervous system. Methods: Eight patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogendeaminase activity, neuropathic patterns, serial changes in nerve conduction studies (NCS), and temporal relationship of central nervous system involvement. Results: Six patients diagnosed with AIP <2 months after symptom onset had neuropathy that was predominantly upper extremity, motor, and proximal. NCS recovery rates were slower in the lower than the upper limbs. Two patients diagnosed >2 months after symptom onset had distal sensorimotor polyneuropathy. Conclusions: The findings from this case series suggest that the peripheral nerves may be differentially and selectively involved in different diagnostic stages of porphyric neuropathy. Muscle Nerve 51: 363-369, 2015 [ABSTRACT FROM AUTHOR]

Objective To investigate clinical and radiological features of Tolosa- Hunt syndrome ( THS) and examine their diagnostic value, and to propose clinical and radiological features that indicate other symptomatic painful ophthalmoplegias ( SPOs) in order to distinguish them from THS. Background Clinical presentations of THS are nonspecific and may overlap with many etiologies. Therefore, excluding other SPOs is essential for correct diagnosis. At the present time, the predictive value of the current International Classification of Headache Disorders ( ICHD) criteria is not well established, and specific imaging markers that can discriminate SPOs from THS are lacking. Methods Patients referred with painful ophthalmoplegia over 12 years were recruited retrospectively and allocated into THS or SPO groups. Typical symptoms (episodic unilateral orbital pain preceding or developing with diplopia) and imaging of THS (inflammatory lesions in the cavernous sinus/orbit by magnetic resonance imaging) were proposed based on ICHD-3 beta criteria and previous literature. Atypical clinical and radiological features suggesting alternative diagnoses were also proposed to predict SPO. Initial presentations and imaging findings were registered and correlated with diagnostic outcomes. The predictive value of clinical and imaging findings was then evaluated. Results Of the 61 referred cases, 25 were classified as THS and 36 as SPO. Of the SPO cases, 52.8% manifested typical THS symptoms at onset. Patients with SPOs were prone to have atypical symptoms (47.2%) and radiographical findings (82.1%) in comparison to those with THS (4.0% and 4.2%, respectively; both P < .001). Both typical symptoms and imaging findings predicted a diagnosis of THS with high sensitivity (95.8% and 100%, respectively) but low specificity (47.2% and 28.6%, respectively). High sensitivity (82.1%) and specificity (95.8%) were achieved using atypical imaging features to predict SPO. Conclusion A diagnosis of THS based strictly on clinical presentations or imaging results is not completely reliable. Identification of atypical imaging features may have a useful role in discriminating SPOs and thus avoid erroneous diagnoses of THS. Future studies with larger sample sizes are warranted to evaluate their validity in general population. [ABSTRACT FROM AUTHOR]

Background: Motor and somatosensory evoked potentials (MEPs and SSEPs) are sensitive tools for detecting subclinical lesions, assessing disease severity, and determining the prognosis for outcomes of patients with inflammatory neurological diseases such as multiple sclerosis. However, their roles in neuromyelitis optica (NMO), a severe inflammatory neurological disease that predominantly involves optic nerves and spinal cord, have not yet been clarified. Methods and Findings: Clinical symptoms and examination findings at relapses of 30 NMO patients were retrospectively reviewed. Abnormal MEPs were observed in 69.2% of patients. Patients with abnormal motor central conduction time (CCT) of the lower limbs had higher Kurtzke Expanded Disability Status Scale (EDSS) scores than those with normal responses (P = 0.027). Abnormal SSEPs were found in 69.0% of patients. Patients with abnormal lower limb sensory CCT had higher EDSS scores than those with normal responses (P = 0.019). In 28 patients followed up more than 6 months, only one of 11 patients (9.1%) with normal SSEPs of the lower limbs had new relapses within 6 months, whereas 8 of 17 patients (47.1%, P = 0.049) with abnormal SSEPs of the lower limbs had new relapses. Conclusions: These results indicate MEPs and SSEPs of the lower limbs are good indicators for the disability status at relapses of NMO. Lower limb SSEPs may be a good tool for reflecting the frequency of relapses of NMO. [ABSTRACT FROM AUTHOR]

Objective: To report detailed motor conduction findings on Fisher syndrome (FS). Methods: We retrospectively reviewed motor conduction findings of 55 patients with pure FS and compared them with those obtained from 83 age- and sex-matched healthy volunteers. Results: In the FS group, distal and F-wave latencies of the median, ulnar, peroneal and tibial nerves were all significantly prolonged; motor conduction velocities were slowed in the median, ulnar and peroneal nerves. Conversely, an abnormally low compound muscle action potential amplitude was found only in the median and tibial nerves. Among the four parameters, distal and F-wave latencies were more frequently encountered abnormalities. None of our patients had abnormal temporal dispersion in any motor nerve. Focal involvement of the ulnar nerve across the elbow segment was observed in 6 patients (11%). Of the 55 FS patients, 31 (56%) had abnormal motor conduction results in at least one nerve. Abnormal motor conduction results were noted in 43 and 61% of patients when the tests were performed in the first week and 1 week after onset of FS, respectively (p = 0.238). Conclusion: Our results confirmed that mild motor conduction abnormalities were noted in pure FS, with a pattern similar to those observed in Guillain-Barré syndrome. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To report sensory conduction findings in patients with typical Fisher syndrome (FS) and to determine if a specific pattern of sensory conduction abnormalities was present in such patients. Methods: We retrospectively reviewed results of sensory conduction studies of 55 FS patients and compared them with those obtained from 83 age- and sex-matched healthy volunteers. Results: Mean median and ulnar sensory nerve action potential (SNAP) amplitudes were lower in FS patients than in normal subjects, whereas sural SNAP amplitudes were not different between the two groups. Abnormal median/ulnar sensory responses (reduced SNAP amplitude or absent response) were more frequently observed than abnormal sural response. Normal sensory conduction results were found in 31 (56%) patients. Of the 24 (44%) patients with abnormal sensory findings, 18 (33%) had a sural-sparing pattern of abnormalities. Patients with impaired sensation had lower median and ulnar SNAP amplitudes than those without. Conclusions: Abnormal median and ulnar sensory responses were the most frequent sensory findings in FS. Findings of the sural-sparing pattern of abnormalities suggest distal sensory nerve involvement in these patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The clinical presentations, MRI findings and outcomes for spinal cord infarction (SCI) are well documented in the West but scarce in the East. We investigated the clinical characteristics of SCI patients and further analyzed etiologies and prognostic factors in Chinese subjects. Methods: We reviewed all SCI patients from March 1993 to March 2007. Clinical symptoms, laboratory and imaging findings as well as outcomes were retrospectively analyzed. Results: Twenty-two patients (12 female) were identified; their mean age was 57.6 years. Nine patients (40.9%) had probable etiologies, while 13 were cryptogenic (59.1%). The primary etiologies were aortic diseases. Hypertension was the most common vascular risk factor (50%). Most patients (10/22 = 45.5%) had thoracolumbar lesions (mainly at T9–L1), while cervical lesions (9/22 = 40.9%) were the second most common (mainly at C4–C7). ‘Owl’s eyes’ signs were common with the anterior spinal artery (93.8%) and central cord infarctions (50%) but not in the posterior spinal artery or transverse spinal infarctions. After a mean follow-up of 18 months, only 10 patients (10/22 = 45%) had good outcomes (independent walking or walking with 1 aid). Conclusion: Most SCI patients had acute, monophasic symptoms, reaching nadir in <24 h. The subjects frequently had acute pain near their lesions before SCI signs/symptoms (16/22 = 72.7%). Initial severe weakness (Medical Research Council score ≤2) and a young age at onset (55 years old) are correlated with poor recovery of motor functions. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this study was to review the clinical manifestations of 40 patients who fulfilled the clinical criteria for Hirayama disease (juvenile muscular atrophy of distal upper extremities), identified in our neuromuscular clinic between February 1995 and December 2005. Of these 40 patients, 87.5% were male. The mean age at onset was 16.8 years, which was 4.5 years later than the peak age of the normal growth curve. Progressive muscle weakness and wasting were characteristic and occurred predominantly in the distal part of the right upper limb. Neurogenic symptoms ceased to progress within 5 years in most patients (92.5%). About one third of patients had participated frequently in heavy physical activity before onset of muscle symptoms. Reduced amplitude of the compound muscle action potential of the ulnar nerve was the most prominent finding in nerve conduction studies. Electromyography showed acute or chronic neurogenic changes, most frequently in muscles supplied by the C7-T1 segments. Magnetic resonance imaging showed anterior shifting of the posterior dura and engorged posterior venous plexus at the cervical level in 95% of patients. Our results support the belief that Hirayama disease is a self-limited, focal lower motor neuron disease involving the lower cervical segments. Disproportionate growth between the vertebral column and the contents of the spinal canal may be the underlying cause, and strenuous physical activity may be a precipitating factor. Muscle Nerve, 2008 [ABSTRACT FROM AUTHOR]

To identify subclinical autonomic dysfunction in mild Guillain-Barré syndrome (GBS), a set of autonomic function tests was serially performed for up to 6 months in 5 GBS patients with mild disability at the nadir. Parasympathetic autonomic function tests consisted of Valsalva ratio and R-R interval variation during rest and deep breathing. Sympathetic autonomic function was evaluated by blood pressure responses to sustained handgrip, hand immersion in ice water, and active standing. The results showed that abnormal parasympathetic and sympathetic function was frequently encountered in all 5 patients during the acute stage of the illness. Autonomic dysfunction occurred both in axonal and demyelinating types of GBS. There was a trend of improvement in most autonomic function tests after 3 months, comparable to the recovery of motor function. In conclusion, subclinical autonomic dysfunction was present in mild GBS. It was temporary and would resolve spontaneously.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Deals with a case of carbofuran poison with delayed neuropathy presented with typical features of anticholinesterase poisoning including impaired consciousness and respiratory failure. Results of sensory and neurologic examinations; Response of the patient to treatment approaches.

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-1β, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs.Methods: A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed.Results: Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients' current age, and the progression rate of disease was positively correlated with age at onset.Conclusions: SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease. [ABSTRACT FROM AUTHOR]

Background: Painful ophthalmoplegia with normal cranial imaging is rare and confined to limited etiologies. In this study, we aimed to elucidate these causes by evaluating clinical presentations and treatment responses.Methods: Cases of painful ophthalmoplegia with normal cranial MRI at a single center between January 2001 and June 2011 were retrospectively reviewed. Diagnoses of painful ophthalmoplegia were made according to the recommendations of the International Headache Society.Results: Of the 58 painful ophthalmoplegia cases (53 patients), 26 (44.8%) were diagnosed as ocular diabetic neuropathy, 27 (46.6%) as benign Tolosa-Hunt syndrome (THS), and 5 (8.6%) as ophthalmoplegic migraine (OM). Patients with ocular diabetic neuropathy were significantly older (62.8 ± 7.8 years) than those with benign THS (56.3 ± 12.0 years) or OM (45.8 ± 23.0 years) (p < 0.05). Cranial nerve involvement was similar among groups. Pupil sparing was dominant in each group. Patients with benign THS and OM responded exquisitely to glucocorticoid treatment with resolved diplopia, whereas patients with ocular diabetic neuropathy didn't (p < 0.05). Patients with OM recovered more rapidly than the other groups did (p < 0.05). Overall, most patients (94.8%) recovered completely during the follow-up period.Conclusions: Ocular diabetic neuropathy and benign THS accounted for most of the painful ophthalmoplegias in patients with normal cranial imaging. Patient outcomes were generally good. [ABSTRACT FROM AUTHOR]

Essential tremor (ET), which is one of the most common movement disorders, may lead to severe interference in quality of life. The first genome-wide association study (GWAS) has identified an association of the LINGO1 variant (rs9652490) with ET in Americans and Europeans. Recently, a second GWAS that was performed in a European population has discovered a new variant (rs3794087) of the main glial glutamate transporter (SLC1A2) that increases the risk of ET with an odds ratio of about 1.4. SLC1A2 encodes for the major glial high-affinity glutamate reuptake transporter in the brain and is a potential ET susceptibility gene. Because replication in a different ethnic population is important for validating a finding, we conducted a case-control study to investigate the SLC1A2 variant in an Asian cohort with ET in Taiwan. A total of 542 subjects (273 ET patients and 269 controls) were included. The results showed that rs3794087 was associated with ET among the Taiwanese. The odds ratio was 1.37. Our results were similar to those of the second GWAS of ET in Europeans, and this confirms that SLC1A2 may be a good functional candidate gene for ET. A replication study in another independent population is of importance to validate this association. [ABSTRACT FROM AUTHOR]