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.

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.

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.

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.

Clinical presentation and electrophysiological findings of porphyric neuropathies: a follow-up study.

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.

Clinical and radiological findings suggesting disorders other than tolosa-hunt syndrome among ophthalmoplegic patients: a retrospective analysis.

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.

Wegener's granulomatosis with nervous system involvement: a hospital-based study.

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.

High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia.

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.

Comparison between the cranial magnetic resonance imaging features of neuromyelitis optica spectrum disorder versus multiple sclerosis in Taiwanese patients.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the central nervous system with different pathogenesis, brain lesion patterns, and treatment strategies. However, it is still difficult to distinguish these two disease entities by neuroimaging studies. Herein, we attempt to differentiate NMOSD from MS by comparing brain lesion patterns on magnetic resonance imaging (MRI). METHODS: The medical records and cranial MRI studies of patients with NMOSD diagnosed according to the 2006 Wingerchuk criteria and the presence of anti-aquaporin 4 (anti-AQP4) antibodies, and patients with MS diagnosed according to the Poser criteria, were retrospectively reviewed. RESULTS: Twenty-five NMOSD and 29 MS patients were recruited. The NMOSD patients became wheelchair dependent earlier than MS patients (log rank test; P = 0.036). Linear ependymal (28% vs. 0%, P = 0.003) and punctate lesions (64% vs. 28%, P = 0.013) were more frequently seen in NMOSD patients. Ten NMOSD patients (40%) had brain lesions that did not meet the Matthews criteria (MS were separated from NMOSD by the presence of at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or the presence of a subcortical U-fiber lesion or a Dawson finger-type lesion). The different image patterns of NMOSD didn't correlate with the clinical prognosis. However, NMOSD patients with more (≧10) brain lesions at onset became wheelchair dependence earlier than those with fewer (<10) brain lesions (log rank test; P < 0.001). CONCLUSIONS: The diagnostic sensitivity of NMOSD criteria can be increased to 56% by combining the presence of linear ependymal lesions with unmet the Matthews criteria. The prognoses of NMOSD and MS are different. A specific imaging marker, the linear ependymal lesion, was present in some NMOSD patients. The diagnosis of NMOSD can be improved by following the evolution of this imaging feature when anti-AQP4 antibody test results are not available.

Painful ophthalmoplegia with normal cranial imaging.

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.

A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome.

BACKGROUND: Tolosa-Hunt syndrome (THS) manifests as a benign or an inflammatory type disease. The nosography differences between these types remain to be elucidated. We aimed to analyze and compare the clinical presentations of benign and inflammatory THS. METHODS: The ward patients who presented with THS from January 1990 to May 2011 were retrospectively reviewed. THS was diagnosed according to the recommendations of the International Headache Society. RESULTS: Of the 53 THS cases (49 patients), 30 (56.6%) were classified as benign and 23 (43.4%) as inflammatory THS. There were strong similarities between the groups in terms of clinical manifestations, laboratory findings, responses to glucocorticoid treatment, and outcomes. However, patients with inflammatory THS tended to be younger (mean age, 43.4 years; P 0.05) and have optic nerve dysfunction (56.5%; P 0.05) and longer disease duration (2.3 ± 1.0 months; P 0.05) compared to those with benign THS (mean age, 56.4 years; mean disease duration, 1.6 ± 0.7 months). The patients with additional involvement of both the optic nerve and the second division of the trigeminal nerve experienced a longer disease duration ( P 0.05). Additionally, patients with orbital pseudotumors had diplopia that responded poorly to treatment with glucocorticoids ( P 0.05). High-dose (>0.5 mg/kg/day) and low-dose (≤0.5 mg/kg/day) prednisolone were equally effective in relieving symptoms in both groups ( P > 0.05). CONCLUSION: Benign and inflammatory THS were highly similar in terms of nosography. The responses to glucocorticoid treatment were generally good except in patients with orbital pseudotumors.

Motor conduction findings in Fisher syndrome.

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.

Sensory conduction study in fisher syndrome: patterns of abnormalities and their clinical correlation.

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.

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.

Electrophysiological features of Hirayama disease.

INTRODUCTION: The purpose of this study was to compare the pattern of hand muscle involvement in Hirayama disease (HD) and amyotrophic lateral sclerosis (ALS). METHODS: We reviewed findings of upper limb nerve conduction studies of 46 HD patients and 60 ALS patients. The findings from 54 healthy subjects were used for comparison. RESULTS: In HD, the ulnar compound muscle action potential (CMAP) amplitude was more severely reduced than the median one, and the reverse pattern was observed in ALS. The mean ulnar/median (U/M) CMAP amplitude ratio was significantly lower in HD (0.64 ± 0.79) and abnormally higher in ALS (2.15 ± 1.77) compared with normal subjects (0.89 ± 0.23). An abnormally low U/M CMAP amplitude ratio (<0.6) was encountered in 34 patients with HD and in 1 with ALS. A U/M CMAP amplitude ratio ≥4.5 or absent median motor response was found only in ALS. CONCLUSION: Our findings demonstrate different patterns of hand muscle involvement between these two diseases.

Clinical characteristics of adult tetanus in a Taiwan medical center.

BACKGROUND/PURPOSE: Despite effective vaccine programs, tetanus is occasionally observed in adults. We reviewed clinical presentation data for adult patients with tetanus in the post-vaccine era in Taiwan. METHODS: We retrospectively reviewed the medical records of all adult patients (age >18 years) discharged from Chang-Gung Memorial Hospital at Lin-Ko (CGMHLK) after treatment for tetanus between January 1996 and July 2005. Data regarding demographic characteristics, clinical manifestation, treatment, and outcome were collected. To assess the features for different age groups, patients were divided into those aged ≥65 years and those aged <65 years. To identify risk factors for respiratory failure, the patients were classified as those with and without respiratory failure. RESULTS: Twenty-three patients with tetanus, 11 (48%) women and 12 (52%) men, were included in the study. The average age was 57 ± 18 years (range 18-84 years). Eighteen (78%) patients had a history of acute injury. The average incubation period was 8 ± 5 days. The most common clinical presentation at onset was trismus (78%). Thirteen (57%) patients developed respiratory failure and underwent endotracheal intubation. The most common complication was pneumonia (30%). All the patients survived and recovered. Age ≥65 years was significantly associated with trismus, dysphagia, dysarthria, and pneumonia. Generalized tetanus subtype and pneumonia were significant risk factors for respiratory failure. CONCLUSION: This study revealed several characteristics of adult tetanus cases in the post-vaccine era in Taiwan. Further serological studies and improved tetanus vaccinations may be needed to ensure better protection, especially for high-risk populations. The exceptionally good prognosis for our patients confirms that appropriate treatment, including wound care, early diagnosis, proper medication, and prevention of complications, is essential in managing this traditional curable disease.

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.

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.