Relationship of tryptophan metabolites with the type and severity of multiple sclerosis.

BACKGROUND: Tryptophan is an essential amino acid primarily metabolized by the kynurenine pathway in mammals. Intermediate metabolites emerging in this pathway have been associated with many neurogenerative diseases. This study aimed to compare tryptophan pathway metabolite levels in patients with multiple sclerosis (MS) and healthy controls and reveal the relationship of tryptophan metabolites with disease subtype and the Expanded Disability Status Scale (EDSS) score. METHODS: The study included a total of 80 MS cases [53 with relapsing remitting MS (RRMS) and 27 with secondary progressive MS (SPMS)] and 41 healthy volunteers. The patients with RRMS were further divided into relapse (RRMS-attack) and non-attack (RRMS-stable) groups. Using liquid chromatography mass spectrometry, tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid levels were measured. The serum metabolite levels of the patient and control groups were compared. In addition, the link and relationship between the EDSS score and disease duration of the patients and their plasma tryptophan metabolite levels were examined. RESULTS: The tryptophan level of the patient group was significantly lower than that of the healthy controls (p<0.05). The kynurenine (105.38±65.43), quinolinic acid (10.42±3.56), kynurenine/tryptophan ratio (0.0218±0.019), and quinolinic acid/kynurenic acid ratio (1.7054±0.96141) of the patients with MS were significantly higher compared to the controls (p<0.05). In the receiver operating characteristic analysis of the power of kynurenine/tryptophan and quinolinic acid/kynurenic acid ratios in predicting the disease, both ratios predicted the diagnosis of MS (area under the curve: 0.793 and 0.645, respectively; p<0.05), albeit at low sensitivity and specificity. The parameters were similar between the RRMS-attack and RRMS-stable patient groups (p>0.05). There was also no significant difference between the RRMS and SPMS patient groups in terms of tryptophan metabolites (p>0.05). Lastly, no significant relationship was observed between tryptophan metabolites and MS subtype and the EDSS score. CONCLUSION: Our findings revealed that the kynurenine pathway involved in the tryptophan metabolism differed between the patients with MS and healthy controls, and this difference may be a limited guide in the diagnosis of MS, due to major overlaps in values for MS versus Controls, and is insufficient to determine the disease subtype.

Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective.

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

Serum ADMA levels were positively correlated with EDSS scores in patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoinflammatory, chronic central nervous system disease. In the pathogenesis of the disease increased nitric oxide (NO) levels play an important role. Nitric oxide (NO) has neuroprotective effects in physiological conditions, however, it is thought that excessive NO formation in MS may lead to demyelination and axonal damage. Derivatives of methylarginine including asymmetric dimethyl arginine (ADMA), L-N monomethyl arginine (L-NMMA), symmetric dimethyl arginine (SDMA) directly or indirectly reduce NO production. Our aim was to measure the levels of methylarginine derivatives and citrulline, ornithine, arginine, homoarginine levels, which are metabolites associated with NO metabolism, in MS subgroups.

Decrease in Pulse Wave Velocity is Associated with Clinical Improvement in Patients with Ischemic Stroke.

BACKGROUND: Arterial stiffness is an independent determinant of cardiovascular and cerebrovascular risks. The relationship between the increase in arterial stiffness parameters and the severity of stroke has been shown in previous studies. We aimed to investigate the association between clinical improvement and changes in arterial stiffness parameters in patients presenting acute ischemic stroke. METHODS: A total of 107 patients were enrolled in this study. On the first and seventh day of the hospitalization, 24 h non-invasive blood pressure was monitored and arterial stiffness parameters were measured. The National Institutes of Health Stroke Scale (NIHSS) was used to determine the severity of stroke, and the Modified Rankin Scale was used to determine dependency and to evaluate functional improvements. RESULTS: Arterial stiffness parameters of augmentation index (AIx@75) and pulse wave velocity (PWV) were significantly higher in patients who died during hospitalization than patients who were discharged (respectively p <0.001, p = 0.04). In the group with clinical improvement, PWV values measured on the seventh day were significantly lower than PWV values measured on the first day (p = 0.032). When the changes in PWV value measured on the first and seventh day for both groups were analyzed using mixed ANOVA test, p value were significant (p = 0.033). Multivariate binary logistic regression analyses showed that negatively change in PWV and CDBP independently predicts the clinical improvement. CONCLUSIONS: Increased AIx@75 and PWV appear to be associated with higher in-hospital mortality rates in patients with acute ischemic stroke. Additionally, clinical improvement in patients with ischemic stroke is associated with a decrease in PWV .

Automatic phase reversal detection in routine EEG.

Electroencephalograph (EEG), a valuable tool in the clinical evaluation, is readily available, safe and provides information about brain function. EEG interpretation is important for the diagnosis of neurological disorders. The long-term EEG data may be required to document and study neurosciences that include many epileptic activities and phase reversal (PR) etc. However, analyze of the long-term EEG done by an expert neurologist is much time consuming and quite difficult. Therefore, an automatic PR determination method for analyzing of long-term EEG is described in this study. The presented technique was applied to the pathological EEG recordings that were obtained from two different datasets gathered as a retrospective in Selcuk University Hospital (SUH) and Boston Children's Hospital (BCH). With this method, PR in the dataset was determined and then compared with the ones detected by the specialist doctor. Two tests were carried out in the SUH dataset and the classification success of the method was 83.22% for test 1 and 85.19% for test 2. On the other hand, three tests were carried out for two different position values for BCH dataset. The highest classification success of the six tests was 75% for test 5, while the lowest classification success appeared as 58.33% for test 6. As a result, the overall success in the detection of PR with the conducted method is 84.20% for SUH and 66.7% for BCH. According to these results, the determination of PR that is known to be indicative of neurological disorders and presenting them to expert information will accelerate the interpretation of long-term EEG recordings.

Arterial stiffness and carotid intima-media thickness in diabetic peripheral neuropathy.

BACKGROUND: We investigated the relationship between peripheral neuropathy and parameters of arterial stiffness and carotid intima media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: The study included 161 patients (80 females and 81 males), 69 of whom had peripheral neuropathy. All patients underwent 24-h blood pressure monitoring, and arterial stiffness parameters were measured. The CIMT was measured using B-mode ultrasonography and patients also underwent transthoracic echocardiographic examination. RESULTS: Patients with peripheral neuropathy, compared with those without it, were older (54.68±8.35 years vs. 51.04±7.89 years; p=0.005) and had T2DM for longer periods (60 vs. 36 months; p=0.004). Glycated hemoglobin (HbA1c) values (8.55±1.85 mg/dL vs. 7.30±1.51 mg/dL; p<0.001), pulse wave velocity (PWV) (7.74±1.14 m/s vs. 7.15±1.10 m/s; p=0.001), CIMT (anterior 0.74±0.15 mm vs. 0.67±0.13 mm; p=0.01), and left ventricular mass (LVM) index (98.68±26.28 g/m2 vs. 89.71±19.70 g/m2; p=0.02) were all significantly increased in the group with peripheral neuropathy compared to the group without peripheral neuropathy. We determined that duration of diabetes, HbA1c, and LVM index were predictors of peripheral neuropathy. CONCLUSIONS: A significant relationship was found between diabetic neuropathy and increased PWV, a parameter of arterial stiffness, as well as CIMT, a marker of systemic atherosclerosis. Diabetic peripheral neuropathy may be a determinant of subclinical atherosclerosis in T2DM.