Analysis of factors correlated with spinal clinically isolated syndrome conversion to multiple sclerosis.

INTRODUCTION: The present study aims to explore the factors influencing spinal clinically isolated syndrome (CIS) conversion to multiple sclerosis (MS). MATERIAL AND METHODS: Sixty-one patients diagnosed with spinal CIS from January 2010 to November 2020 were divided into a non-progressing (CIS) group with 27 patients, and a conversion to MS (MS) group with 34 patients, based on whether they had converted to MS. The clinical presentation at onset, the Expanded Disability Status Scale (EDSS) before and after steroid therapy, the results of magnetic resonance imaging (MRI), the oligoclonal bands in cerebrospinal fluid (CSF-OCB), and the evoked potentials (EPs) were retrospectively analysed. RESULTS: Differences in gender and age were not statistically significant between the MS and CIS groups. The median time to relapse was 12 months for the MS group, with an upper quartile of 23.7 months, and 91.2% of patients relapsed within three years. In univariate analysis, patients with CIS beginning with sensory symptoms had a lower level of progression to MS (OR = 0.311). Patients with Kurtzke Functional Systems Scores (FSSs) of pyramidal functions ≥ 2 (OR = 3.582) and positive CSF-OCB (OR = 5.208) quickly progressed to MS. There was no significant difference between the two groups in terms of spinal cord lesions < 3 vertebral segments, gadolinium enhancing lesions, or abnormal EPs. The difference in the EDSS scores before and after steroid therapy was higher in the MS group than in the CIS group (p = 0.001). Differences of ≥ 1.5 in the EDSS scores before and after steroid therapy were risk factors for CIS conversion to MS (OR = 9.333). CONCLUSIONS: Patients with spinal CIS with pure sensory abnormalities at onset were less likely to convert to MS (OR = 0.311), and the risk factors were, in order of risk, the difference in EDSS score before and after steroid therapy (≥ 1.5; OR = 9.333), positive CSF-OCB (OR = 5.208), and those with an FSS of the pyramidal functions score ≥ 2; OR = 3.582). The present study serves as a simple 'first step'. Any potential predictors identified should be validated via future prospective studies.

Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain.

Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient's pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient's pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioid-induced hyperalgesia in chronic neuropathic pain patients.

[A study of motor unit number estimation by multiple point stimulation in patients with Hirayama disease].

OBJECTIVE: To explore the significance of motor unit number estimation (MUNE) by using multiple point stimulating technique to evaluate patients with Hirayama disease (HD). METHODS: Multiple point stimulating technique was used to estimate the motor unit number of abductor pollicis brevis and abductor digiti minimi in 35 normal subjects [14 - 33 years old, mean (20.9 ± 4.0) years old, 33 men and 2 women] without nerve and muscle disease and 69 patients definitely diagnosed as HD [16 - 35 years old, mean (21.46 ± 6.61) years old, 67 men and 2 women]. The differences between the two groups were examined by Fisher's exact test and t test. RESULTS: There were 42 patients with atrophy and 27 patients with normal clinical manifestation of left hand. For right hand there were 54 patients with atrophy and 15 normal. For controls, the MUNE value of left abductor pollicis brevis was 226.97 ± 30.59, while that of right side was 228.31 ± 25.35. The MUNE value of left abductor digiti minimi was 237.43 ± 30.78, while that of right side was 240.20 ± 37.73. For HD patients, the MUNE of left abductor pollicis brevis and abductor digiti minimi was 145.66 ± 126.10 (t = 5.07, P < 0.01) and 102.20 ± 112.67 (t = 9.31, P < 0.01) respectively, while those of right hand was 149.72 ± 117.80 (t = 5.31, P < 0.01) and 64.23 ± 69.27 (t = 16.76, P < 0.01) respectively. MUNE of left abductor digiti minimi in 17 patients that was below 200 among 27 patients with normal clinical manifestation (χ(2) = 9.57, P = 0.002). MUNE of right abductor digiti minimi in 12 patients that was below 200 among 15 patients with normal clinical manifestation (χ(2) = 4.64, P = 0.03). CONCLUSIONS: The differences of MUNE values by multiple point stimulating technique between the normal subjects and the HD patients is significant, which suggests this method is very useful to evaluate HD in the early state.

[Study of association between hyperIgEaemia and Hirayama disease].

OBJECTIVE: To investigate whether hyperIgEaemia is associated with Hirayama disease in China. METHODS: Serum total IgE were examined in 123 patients and 82 control subjects from 2006 to 2009 at this hospital and their correlations with clinical profiles investigated. The data were analyzed by t, Chi-square and nonparametric tests. RESULTS: Past or present history of allergy/atopy was found in 14 (11.4%) patients and 11(13.4%)controls. The median value of serum total IgE were 87.97, 59.21 and 51.39 IU/ml in patients, controls and health controls respectively. There were no significant difference between the patient and control groups (Z = -0.947, P = 0.344) and the health control groups (Z = -0.914, P = 0.361). Serum IgE was elevated in 57 (43.6%) patients and 30 (36.6%) controls. HyperIgEaemia was present in 29 (23.6%) patients and 13 (15.9%) controls. There was no significant difference in the frequency of history of allergy/atopy, IgE elevation or hyperIgEaemia (P > 0.05) between cases and controls. Even after analyzing the length of duration or the severity of clinical disabilities, there was no difference neither (P > 0.05). CONCLUSION: Whether the length of duration or the severity of clinical disabilities, the serum total IgE level has no significant difference between all groups. HyperIgEaemia is not associated with Hirayama disease.

Identification of alpha-D-glucose-1-phosphate cytidylyltransferase involved in Ebosin biosynthesis of Streptomyces sp. 139.

Ebosin, a novel exopolysaccharide produced by Streptomyces sp. 139 has antagonist activity for IL-1R in vitro and remarkable anti-rheumatic arthritis activity in vivo. Its biosynthesis gene cluster (ste) has been identified. In this study, gene ste17 was expressed in Escherichia coli BL21 and the recombinant protein was purified. With CTP and alpha-D-glucose-1-phosphate as substrates, the recombinant Ste17 protein was found capable of catalyzing the production of CDP-D-glucose and pyrophosphate, demonstrating its identity as an alpha-D-glucose-1-phosphate-cytidylyltransferase (CDP-D-glucose synthase). To investigate the function of ste17 in Ebosin biosynthesis, the gene was disrupted with a double crossover via homologous recombination. The monosaccharide composition of exopolysaccharide (EPS) produced by the mutant Streptomyces sp. 139 (ste17 (-)) was found significantly altered from that of Ebosin, with glucose becoming undetectable. This gene knockout also negatively affected the antagonist activity for IL-1R of EPS. These results indicate that the CDP-D: -glucose synthase encoded by ste17 gene is involved in the formation of nucleotide sugar (CDP-D-glucose) as glucose precursor in Ebosin biosynthesis.

Knockout of the gene (ste15) encoding a glycosyltransferase and its function in biosynthesis of exopolysaccharide in Streptomyces sp. 139.

Streptomyces sp. 139 produces a novel exopolysaccharide (EPS) designated Ebosin which has antagonistic activity for IL-1R in vitro and remarkable anti-rheumatic arthritis activity in vivo. We previously identified a ste (Streptomyces eps) gene cluster consisting of 27 ORFs responsible for Ebosin biosynthesis. The gene product of ste15 shows high homology to known glycosyltransferases (GTFs). To elucidate its function in Ebosin biosynthesis, the ste15 gene was knocked out with a double crossover via homologous recombination. Our analysis of monosaccharide composition for EPS-m produced by the mutant strain Streptomyces sp. 139 (ste15(-)) showed that glucose was significantly diminished compared to its natural counterpart Ebosin. This derivative of Ebosin lost the antagonistic activity for IL-1R in vitro and its molecular mass was smaller than Ebosin. These results have demonstrated that the ste15 gene codes for a GTF for glucose, which is functionally involved in Ebosin biosynthesis.