Serkan Kirbas

Retinal nerve fiber layer thickness in Parkinson disease.

Abstract:Dopaminergic neuronal cells have been identified in the inner nuclear and inner plexiform layers of the human retina. The dopaminergic content of the retina is reduced in patients with idiopathic Parkinson disease (PD). These observations led us to study the retinal nerve fiber layer (RNFL) thickness in patients with PD without visual impairment compared to healthy controls using spectral-domain optical coherence tomography (SD-OCT). Eighty-two subjects, including 42 patients with PD, newly diagnosed and untreated (24 men, 18 women, age range: 47–66 years), and 40 healthy controls, were enrolled. Both eyes of patients with PD and controls were imaged with SD-OCT. The mean RNFL thickness was 77 ± 11.5 &mgr;m in PD patients and 89 ± 8.7 &mgr;m in healthy controls (P = 0.001). Selective thinning of the RNFL was found in the temporal region with mean temporal RNFL thickness of 66 ± 6.7 &mgr;m in PD patients and 75 ± 4.8 &mgr;m in controls (P = 0.001). The thickness of the RNFL is decreased in PD patients. Demonstrating progressive thinning of RNFL over time will be critical for validating optical coherence tomography as a viable biomarker of patients with PD.

Low-density lipoprotein subfraction, carotid artery intima-media thickness, nitric oxide, and tumor necrosis factor alpha are associated with newly diagnosed ischemic stroke.

Objectives: Small dense (sd) low-density lipoprotein (LDL), tumor necrosis factor (TNF) alpha (α), and nitric oxide (NO) have recently emerged as important stroke risk factors. The aim of the study was to investigate the effects of increased levels of small LDL particle size, TNF-α and NO on the developed ischemic stroke and increased carotid artery intima-media thickness (CIMT). Materials and Methods: A total of 29 women and 25 men (a total of 54 ischemic stroke patients) and a similar age group of 50 controls (29 females and 21 males) were included in the study. CIMT, C-reactive protein (CRP), TNF-α, NO, and lipid subfraction test of the two groups were measured. Results: The mean LDL particle size was smaller in patients with stroke than in the controls (26.8 ± 0.31 nm vs. 27.0 ± 0.31 nm, P = 0.003). sd-LDL, TNF-α, NO, CRP, right CIMT, and left CIMT were higher in patients with stroke than in the controls (respectively; 8.2 ± 7.8 mg/dL vs. 3.3 ± 3.5 mg/dL, P < 0.001;75.6 ± 25.0 pg/mL vs. 65.4 ± 9.1 pg/mL, P = 0.009;76.4 ± 53.3 mmol/L vs. 41.5 ± 27.0 mmol/L, P < 0.001;1.9 ± 2.6 mm vs. 0.4 ± 0.3 mm P < 0.001;0.97 ± 0.38 mm vs. 0.83 ± 0.15 mm, P = 0.007;1.04 ± 0.44 mm vs. 0.87 ± 0.19 mm, P = 0.010). Conclusion: These results show that sd-LDL is independently associated with the incidence of stroke and may be a risk factor in the development of stroke. In addition, TNF-α, NO, right CIMT, and left CIMT may be a risk factor in the development of ischemic stroke.

Paraoxonase and arylesterase activity and total oxidative/anti-oxidative status in patients with idiopathic Parkinson's disease.

This study investigated serum paraoxonase (PON1) and arylesterase activity along with determination of oxidative status via measurement of total oxidant status (TOS), total anti-oxidant status (TAS) and oxidative stress index (OSI) in patients with Parkinsons disease (PD) and compared results with data from healthy controls. A total of 82 subjects, including 42 patients with idiopathic PD, newly diagnosed and untreated (24 men, 18 women, aged 47-66 years) and 40 healthy controls were enrolled in this study. We aimed to evaluate the oxidative status of PD patients via measurement of serum TOS and TAS and estimation of OSI using new automated methods. PON1 and arylesterase activities were measured spectrophotometrically. Serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride levels were measured using routine methods. TAS levels of PD patients were significantly lower than that of controls (p<0.05). TOS levels of PD patients were higher than those of controls (p<0.05). PON1 and arylesterase activities of PD were lower than those of controls (p<0.05). Serum levels of total and LDL cholesterol were significantly reduced in PD patients. In conclusion, the presence of high TOS and OSI levels together with low levels of TAS in PD patients supports the important role of oxidative stress in the pathophysiology of PD. Since oxidative stress is involved in neurodegeneration, selecting anti-oxidants, metal chelators or other compounds boosting endogenous enzymatic and non-enzymatic defense mechanisms seems to be an obvious choice as treatment for PD.

Serum paraoxonase and arylesterase activity and oxidative status in patients with multiple sclerosis

The aim of this study was to investigate serum paraoxonase and arylesterase activities, and to determine oxidative status via the measurement of total oxidant status (TOS), total antioxidant status (TAS) and the oxidative stress index (OSI) in patients with relapsing-remitting multiple sclerosis (RRMS). Results were compared with data from healthy controls. A total of 60 subjects, including 30 newly diagnosed and untreated patients with RRMS (20 females, 10 males, 18-40 years of age) and 30 healthy controls (20 female, 10 male 20-40 years of age) were enrolled in this study. The oxidative status of the RRMS patients was measured by TOS, TAS and estimation of the OSI was made by a new automated method. Paraoxonase (PON1) and arylesterase activities were measured spectrophotometrically. TAS levels of RRMS patients were significantly lower than that of controls (p < 0.05). TOS levels of RRMS patients were higher than that of controls (p < 0.05). PON1 and arylesterase activities of RRMS patients were lower, but not significantly, than those of controls (p > 0.05). There was no correlation between serum PON1 activity and OSİ in patients with RRMS (p > 0.05). Hypercholesterolemia was not observed in multiple sclerosis patients. In conclusion, although the mechanism underlying the significant reduction of TAS levels of multiple sclerosis patients compared with those of controls is unknown, the results imply that endogenous antioxidants may have been exhausted by increased oxidative stress and we believe that additional antioxidant treatment might be beneficial for these patients.

Serum levels of homocysteine, asymmetric dimethylarginine and nitric oxide in patients with Parkinson's disease.

Objectives: Endothelial dysfunction has been implicated as a crucial event in the development of several neurodegenerative diseases. The aim of this study was to investigate the serum homocysteine, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) levels in patients with Parkinson’s disease (PD) and to compare the results with data from healthy controls. Methods: A total of 132 subjects, including 82 idiopathic PD patients who were newly diagnosed and untreated (47 males, 35 females, mean age of 60.8 ± 7.1 years) and 50 healthy controls (28 males, 22 females, mean age of 60.2 ± 6.7 years) were enrolled in this study. The serum ADMA and NO levels were determined using enzyme-linked immunosorbent assay (ELISA), while the homocysteine levels were determined by chemiluminescent microparticle immunoassay. Results: The ADMA and NO levels of the PD patients were significantly higher than those of the healthy controls. The serum ADMA levels were 0.70 ± 0.15 μmol/L in the PD patients and 0.50 ± 0.12 μmol/L in the healthy controls (p < 0.001). The serum NO levels were 78.7 ± 10.3 μmol/L in the PD patients and 59.9 ± 9.5 μmol/L in the healthy controls (p < 0.001). In addition, the ADMA and NO levels were significantly correlated with the serum homocysteine levels in patients with PD (r = 0.874, p < 0.001, r = 0.803, p = 0.005, respectively). Conclusion: In our study, the high ADMA and NO levels of patients with PD indicate endothelial dysfunction, and this dysfunction may play a role in PD pathogenesis. Larger studies, including randomised clinical trials in humans and animal studies, are needed to validate our findings and help in developing a better understanding of the pathogenesis of PD.

Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Patients With Vitamin B12 Deficiency Using Spectral Domain Optical Coherence Tomography

Purpose: To compare peripapillary retinal nerve fiber layer (RNFL) thicknesses measured by Cirrus HD optical coherence tomography (OCT) of patients with vitamin B12 deficiency with healthy controls and to evaluate the correlation between the peripapillary RNFL thickness and plasma vitamin B12 levels. Materials and Methods: Forty-five patients (19 male and 26 female) with a diagnosis of vitamin B12 deficiency (patient group) and 45 age- and sex- matched healthy subjects (control group) were consecutively enrolled in this study. Average, temporal, nasal, inferior, and superior quadrant peripapillary RNFL thicknesses of each subject were obtained using the Cirrus HD OCT. Disc area (DA) and rim area (RA), central subfield thickness (CST), cube volume (CV), and cube average thickness (CAT) were also measured. Results: Mean age of each group was 33.1 ± 6.5 years (range: 21–45 years). Mean plasma vitamin B12 level was 114.8 ± 34.0 pg/mL in the patient group and was 405.1 ± 20.0 pg/mL in the control group (p < 0.001). The patient and control groups were similar regarding axial length, plasma folate levels, DA, RA, CST, CV, CAT, and RNFL thicknesses in superior, nasal, and inferior quadrants. However, average RNFL and RNFL in temporal quadrant were significantly thinner in the patient group than in the control group (p = 0.013 and p < 0.001, respectively). In addition, temporal (r = 0.356, p = 0.001) and average (r = 0.212, p = 0.045) peripapillary RNFL thicknesses were correlated with plasma vitamin B12 levels. Conclusion: We have shown that, as in other non-glaucomatous optic neuropathies, temporal quadrant RNFL thickness was thinner in patients with vitamin B12 deficiency and it was correlated with plasma vitamin B12 levels. Further studies are warranted to clarify the clinical relevance of these findings and the effects of vitamin B12 replacement therapy.

Increased pulse wave velocity and carotid intima-media thickness in patients with carpal tunnel syndrome.

Introduction: Carpal tunnel syndrome (CTS) is associated with cardiovascular risk factors. The aim of our study was to determine whether carotid intima–media thickness (CIMT) and carotid–femoral pulse wave velocity (cf‐PWV), as surrogates of cardiovascular disease and arterial stiffness, are increased in patients with carpal tunnel syndrome. Methods: Forty patients with CTS and 40 gender‐ and age‐matched controls underwent cf‐PWV assessment, CIMT measurement, and nerve conduction study. Results: CIMT and cf‐PWV were increased significantly in patients with CTS. They correlated positively with median sensory and motor nerve distal latency. Whereas both CIMT and PWV related to CTS, only CIMT independently predicted CTS. Conclusions: There is both increased pulse wave velocity and CIMT and a positive correlation between these parameters and median nerve sensory distal latency in patients with CTS. CTS appears to be associated with arterial stiffness and atherosclerotic burden, but the underlying mechanisms require further study. Muscle Nerve 47: 872–877, 2013

Effects of lisinopril on NMDA receptor subunits 2A and 2B levels in the hippocampus of rats with l-NAME-induced hypertension

Hypertension is major risk factor leading to cerebrovascular pathologies. N-methyl d-aspartate receptors (NMDARs) and renin-angiotensin system are involved in neuronal plasticity, as well as cognitive functions in the hippocampus. In this study, we examined the effects of lisinopril, an ACE inhibitor, on the levels of hippocampal NMDAR subunits; NR2A and NR2B in l-NAME (Nϵ-nitro-l-arginine Methyl Ester)-induced hypertensive rats. In addition, malondialdehyde (MDA) levels were measured as a marker for lipid peroxidation. Compared with the control group, the MDA level was significantly increased after 8 weeks in the l-NAME-treated group. Rats treated with lisinopril and l-NAME plus lisinopril were found to have significantly decreased hippocampal MDA levels. Regarding the hippocampal concentrations of NR2A and NR2B, there were no statistically significant differences between groups. We demonstrated that lisinopril treatment has no direct regulatory effect on the levels of NR2A and NR2B in the rat hippocampus. Our results showed that Lisinopril could act as an antioxidant agent against hypertension-induced oxidative stress in rat hippocampus. The findings support that the use of lisinopril may offer a good alternative in the treatment of hypertension by reducing not only blood pressure but also prevent hypertensive complications in the brain.

The Impact of Fibromyalgia on Disability, Anxiety, Depression, Sleep Disturbance, and Quality of Life in Patients with Migraine

Introduction The aim of the present study was to assess the impact of fibromyalgia (FM) comorbidity on disability, anxiety, depression, sleep disturbance, and quality of life in patients with migraine. Methods Eighty-six consecutive migraine patients (age, 35.4±10.3 years; 69 women and 17 men) were enrolled in the study. The headache characteristics of the patients were recorded. FM was diagnosed based on the 1990 American College of Rheumatology classification criteria for the diagnosis of FM. All patients were asked to complete selfreport questionnaires, including the Fibromyalgia Impact Questionnaire (FIQ), Headache Impact Test (HIT-6), Migraine Disability Assessment Questionnaire (MIDAS), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and the 36- Item Short Form Survey (SF-36) to assess their pain-related disability, migraine-related disability, depression, anxiety, sleep disturbance, and quality of life. Results Of the migraine patients, 28 (32.6%) met the criteria for FM. Migraine patients with FM showed significantly increased migraine frequency and BDI, BAI, and PSQI scores and decreased quality of life scores for all eight domains of the SF-36 compared to patients with migraine alone, whereas the mean HIT-6 and MIDAS values did not differ between the groups. FIQ score showed statistically significant positive correlations with BDI, BAI, PSQI, and MIDAS scores and with headache frequency (p<0.001, r=0.657; p<0.001, r=0.730; p<0.001, r=0.754; p=0.005, r=0.300; p=0.008, r=0.286, respectively); FIQ score showed negative correlations with scores for all domains of the SF-36. In multivariate linear regression analysis, BDI, BAI, and PSQI scores independently predicted FIQ score. Conclusion Our study results demonstrate the significant impact of FM comorbidity on anxiety, depression, sleep disturbance, and quality of life in this population. FM evaluation and treatment should be considered in the routine care of patients with migraine to globally improve the patients quality of life.

Response to a Letter to the Editor Entitled “Low Serum B12 Level Does Not Mean Vit. B12 Deficiency-Problems Related to the Diagnosis of Vitamin B12 Deficiency”

We thank Dr Grzybowski for the interest he has shown in our article entitled ‘‘Evaluation of peripapillary retinal nerve fiber layer thickness in patients with vitamin B12 deficiency using spectral domain optical coherence tomography’’. Firstly, Dr Grzybowski argues that low serum vitamin B12 level is not automatically diagnostic for vitamin B12 deficiency in asymptomatic, hematologically normal patients. He states that the clinical picture is crucial for determination of the vitamin B12 deficiency. In addition, he says that the levels of the other biomarkers such as methylmalonic acid or homocysteine could be used for the diagnosis. In our study, we used serum vitamin B12 levels, clinico-electrophysiological evaluation and spinal magnetic resonance imaging for the diagnosis of vitamin B12 deficiency and related neuropathies. Eight patients had clinical vitamin B12 deficiency. However, the rest of the patients (37 patients) had subclinical cobalamin deficiency (SCCD). They were hematologically normal patients and they had no clinical signs except for the low serum vitamin B12 levels. It is known that the anemia is not seen in the SCCD. Biochemical markers of cobalamin status have largely confirmatory roles in the diagnosis of clinical deficiency of vitamin B12, whose clinical expressions provide the diagnostic quasi-gold standard. Cobalamin measurement is generally sufficient for the diagnosis because it has more than 90–95% sensitivity in the clinical deficiency. On the other hand, the diagnosis of SCCD depends completely on metabolic testing because the patients are clinically normal. However, the optimal testing for diagnosis of SCCD continues to be investigated. As recently reported, all biomarkers can produce falsely abnormal results, and none is a diagnostic gold standard. Secondly, Dr Grzybowski points out that the reason for vitamin B12 deficiency in our patients was not given and intrinsic factor (IF)-related malabsorption was not verified. The cause of vitamin B12 deficiency and IF was not evaluated in our work because it has been shown that the causes of SCCD are unknown in more than 60% of cases. As Dr Grzybowski states, there are some problems with the diagnosis of vitamin B12 diagnosis. He has enriched our article by discussing these problems throughout his letter. We, sincerely thank him for his contribution to our work.