A database for screening and registering late onset Pompe disease in Turkey.

The aim of this study was to search for the frequency of late onset Pompe disease (LOPD) among patients who had a myopathy with unknown diagnosis registered in the pre-diagnostic part of a novel registry for LOPD within a collaborative study of neurologists working throughout Turkey. Included in the study were 350 patients older than 18 years who have a myopathic syndrome without a proven diagnosis by serum creatine kinase (CK) levels, electrodiagnostic studies, and/or muscle pathology, and/or genetic tests for myopathies other than LOPD. Acid alpha glucosidase (GAA) in dried blood spot was measured in each patient at two different university laboratories. LOPD was confirmed by mutation analysis in patients with decreased GAA levels from either both or one of the laboratories. Pre-diagnostic data, recorded by 45 investigators from 32 centers on 350 patients revealed low GAA levels in a total of 21 patients; from both laboratories in 6 and from either one of the laboratories in 15. Among them, genetic testing proved LOPD in 3 of 6 patients and 1 of 15 patients with decreased GAA levels from both or one of the laboratories respectively. Registry was transferred to Turkish Neurological Association after completion of the study for possible future use and development. Our collaborative study enabled collection of a considerable amount of data on the registry in a short time. GAA levels by dried blood spot even from two different laboratories in the same patient may not prove LOPD. LOPD seemed to be rarer in Turkey than in Europe.

Assessment of the Presence of Carpal Tunnel Syndrome in Patients with Diabetes Mellitus, Hypothyroidism and Acromegaly.

INTRODUCTION: Carpal tunnel syndrome (CTS) is one of the most common entrapment neuropathies of the upper limbs. It results from compromised median nerve function of the wrist that is caused by increased pressure in the carpal tunnel. Repetitive use of the hand and wrist, obesity, pregnancy, rheumatoid diseases, trauma and endocrinopathies are some of the risk factors for CTS. AIM: The purpose of this study was to find out whether patients with diabetes mellitus (DM), hypothyroidism and acromegaly have an increased incidence of carpal tunnel syndrome compared to each other and normal population. MATERIALS AND METHODS: Patients were assigned into three groups as follows: patients with type II DM n: 100, patients with hypothyroidism n:48 and patients with acromegaly n:36. In addition, 50 healthy individuals were included in the study as control subjects. Patients were asked if they had any pain, symptoms of paraesthesia and numbness. Patients with peripheral neuropathy were excluded from the study. Boston Symptom Severity Scale and Functional Capacity Scale were used to assess symptom severity and functional capacity. CTS was investigated by performing electrophysiological study for both hands. RESULTS: The incidence of CTS was significantly higher in all three groups compared to the control group (p>0.05). In addition, the incidence of CTS was significantly higher in the DM group compared to the hypothyroid and acromegaly groups (p<0.001). The incidence of bilateral CTS in the DM group was significantly higher compared to both hypothyroid and acromegaly groups and the control group (p<0.001). CONCLUSION: CTS has a higher incidence in DM, hypothyroid and acromegaly patients compared to healthy individuals. Clinicians should be careful about development of CTS in DM, hypothyroidism and acromegaly. They should adopt a multidisciplinary approach and co-operate with the psychiatrist.

Evaluation of serum oxidant/antioxidant balance in multiple sclerosis.

The total oxidative status (TOS)/total anti-oxidative status (TAS) ratio can provide information on an individual's absolute oxidative stress index (OSI). We investigated the alterations in the oxidant-antioxidant balance by measuring the oxidant parameters OSI, TOS, and malondialdehyde (MDA) together with the antioxidant parameters such as TAS, and superoxide dismutase (SOD) in patients with relapsing remitting multiple sclerosis (MS). To our knowledge, this is the first study to evaluate OSI in patients with relapsing remitting MS. 35 ambulatory patients with relapsing-remitting MS (35.8 ± 8.7 years) and 32 age- and activity-matched healthy control subjects (35.1 ± 3.7 years) that participated in the study. Serum TAS and TOS levels were determined using new automated methods. MS patients had higher concentrations of MDA (151.5 ± 51.1 vs. 111.3 ± 27.4 nmol/g protein, respectively; p < 0.001), TOS (148.1 ± 162.5 vs. 48.3 ± 46.4 mmol H(2)O(2) Equiv./g protein, respectively; p = 0.002), OSI (21124 ± 32543 vs. 5294 ± 5562, respectively; p = 0.008), and SOD (4.5 ± 0.7 vs. 3.4 ± 0.6 U/L, respectively; p < 0.001) compared with healthy controls. On the other hand, MS patients had lower concentrations of NO (12.3 ± 6.9 vs. 17.4 ± 2.5 µmol/g protein, respectively; p < 0.001) and TAS (0.82 ± 0.27 vs. 0.26 ± 0.15, respectively; p = 0.011) compared with healthy controls. In conclusion, these findings indicate that the oxidative stress plays an important role in the pathogenesis of MS.

Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats.

To date, there have not been enough studies about the effects of curcumin against oxidative stress on sciatic nerves caused by streptozotocin (STZ) in diabetic rats. Therefore, this study was undertaken to determine whether curcumin, by virtue of its antioxidant properties, could affect the oxidant/antioxidant balance in the sciatic nerve and brain tissues of streptozotocin (STZ)-induced diabetic rats. A total of 28 rats were randomly divided into four groups of seven rats each: normal controls, only curcumin treated, diabetic controls, and diabetics treated with curcumin. Biomarkers-malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and NO levels-for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. We found a significant increase in MDA, NO, TOS, and OSI, along with a reduction in TAS levels in the brains and sciatic nerves of the STZ-induced diabetic rats (for both parameters p < 0.05). The MDA, TOS, OSI, and NO levels in these tissues were significantly reduced in the curcumin-treated diabetic group compared to the untreated diabetic group. In conclusion, the results of this study suggested that curcumin exhibits neuroprotective effects against oxidative damage in the brain and sciatic tissues of diabetic rats.

Diagnostic value of F-wave inversion in patients with early carpal tunnel syndrome.

Routine electrophysiological studies usually give normal results in patients with early stage carpal tunnel syndrome (CTS). Diagnostic significance of the F-wave inversion (the median of F-wave minimal latencies (FWML) exceeds a normal ipsilateral ulnar FWML by 1ms) has not been previously reported in early stage CTS. In this study, our primary aim was to investigate the diagnostic value of F-wave inversion in early stage CTS. Additionally, we aimed to demonstrate any possible relationship between F-wave inversion and symptom scores of the Boston questionnaire and functional capacity in early stage CTS. The study included 60 early stage CTS patients who presented with a median sensory nerve conduction velocity of ≥50m/s. The symptom severity and functional status of the patients were assessed by using the Boston questionnaire. The control group consisted of 45 healthy volunteers. We compared early stage CTS patients and healthy control subjects in terms of the results obtained from median-ulnar FWML. Existence of F-wave inversion was found in 32 (53.3%) of the early stage CTS patients and in 3 (8.7%) of the healthy controls (p=0.001). It was also found to be positively correlated with the Boston questionnaire scores (p=0.001, r=0.41) and functional capacity scores (p=0.001, r=0.41). The sensitivity and specificity of F-wave inversion for the diagnosis of early stage CTS were calculated as 53.3% and 93.3%, respectively. The addition of F-wave inversion measurement to the set of the routine nerve conduction studies can increase the reliability of the electrophysiological studies in patients with early stage CTS.

Serum levels of calcification inhibitors in patients with intracerebral hemorrhage.

The vascular calcification regulators and inflammatory markers including fetuin-A, osteopontin (OPN), and matrix Gla protein (MGP) may play an important role in the development of intracerebral hemorrhages (ICHs). So far, the relationship between these parameters and ICH has not been studied. Therefore, this study was designed to elucidate whether fetuin-A, MGP, and OPN are involved in the pathophysiology of ICH. The ICH group consisted of 27 consecutive patients with spontaneous ICH evaluated in the neurology intensive care unit within the first 24 hours from the onset of the stroke. The serum OPN levels were significantly increased in patients with ICH compared to the controls. On the other hand, the serum MGP and fetuin-A levels were significantly decreased in the patients with ICH in comparison to the controls. In the patients with ICH, the serum MGP levels of the nonsurvivors were statistically significantly lower than the MGP levels of the survivors. In conclusion, the change in serum fetuin-A, MGP, and OPN levels after ICH indicates that these parameters play a role in the pathophysiological processes leading to an ICH. Measurement of the serum MGP levels may also be of value to estimate mortality.

The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats.

The aim of this experiment was to investigate whether nebivolol and zofenopril have protective effects against oxidative damage and apoptosis induced by cerebral ischemia/reperfusion (I/R). There were seven groups of rats, with each containing eight rats. The groups were: the control group, I/R group, I/R plus zofenopril, I/R plus nebivolol, I/R plus nebivolol and zofenopril, zofenopril only and nebivolol only. Cerebral I/R was induced by clamping the bilateral common carotid artery and through hypotension. The rats were sacrificed 1h after ischemia, and histopathological and biochemical analyses were carried out on their brains. The total antioxidant capacity was evaluated by using an automated and colorimetric measurement method developed by Erel. I/R produced a significant increase in the levels of total oxidant status and malondialdehyde levels, the number of caspase-3 immunopositive cells and activities of prolidase and paraoxonase in brain when compared with the control group (p<0.05). A significant decrease in brain total antioxidant capacity and nitric oxide levels were found in I/R group when compared with the control group (p<0.05). Both nebivolol and zofenopril treatment prevented decreasing of the total antioxidant capacity and nitric oxide levels, produced by I/R in the brain (p<0.05). Both nebivolol and zofenopril treatment prevented the total oxidant status, malondialdehyde levels, activities of paraoxonase and prolidase from increasing in brains of rats exposed to I/R (p<0.05). In conclusion, both nebivolol and zofenopril protected rats from ischemia-induced brain injury. The protection may be due to the indirect prevention of oxidative stress and apoptosis.

Serum prolidase activity and oxidative status in patients with diabetic neuropathy.

We found no data in the literature related to oxidative stress index (OSI), total oxidative status (TOS) and prolidase activity in patients with diabetic neuropathy (DN). In this study, we aimed to evaluate the oxidative status of DN patients via measurement of TOS and serum total antioxidant status (TAS) and estimation of OSI using new automated methods. Thirty-eight healthy participants, 40 diabetic patients without neuropathy, and 39 patients with DN were included. Electrophysiological and neurological examinations were performed. The activity of prolidase and levels of TOS and TAS were determined in the serum of patients. The level of TAS was lower, while the levels of TOS and OSI, and activity of prolidase were higher in both DN and diabetic control groups compared with the healthy subjects (p < 0.05). Prolidase activity was found to be higher in the DN group than in the diabetic control group (p = 0.001). In conclusion, the presence of high TOS and OSI levels together with low levels of TAS in diabetic patients with or without neuropathy may support a role of oxidative stress in the pathogenesis of diabetes mellitus. In addition, increased serum prolidase activity in DN may be interpreted as evidence of increased collagen turnover.

Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine.

Asymmetric dimethylarginine (ADMA) has been found as correlated with endothelial dysfunction and oxidative stress. There are few studies regarding ADMA and nitric oxide (NO) levels in patients with migraine and alterations of ADMA and NO levels during migraine attack are not well-known. Therefore, in present study, we aimed to measure NO and ADMA levels in patients with migraine and compare them with the control group to investigate the correlation between migraine, oxidative stress and endothelial dysfunction. The migraine group consisted of 59 patients, including 22 suffering from migraine with aura and 37 suffering from migraine without aura. The control group consisted of 31 healthy volunteers without headache. The patients in migraine group were divided into subgroups based on whether attack period was present or not and whether it was migraine with or without aura. Plasma ADMA levels were measured using an enzyme-linked immunosorbent assay method. Migraine patients had higher concentrations of NO (35.6±7.7, 31.0±6.2 µmol/L, respectively, p=0.005) and ADMA (0.409±0.028, 0.381±0.044 µmol/L, respectively, p = 0.001) levels when compared with the healthy controls. During migraine attack, NO and ADMA levels were found to be significantly higher in migraine group as compared to control group (respectively, p=0.015, p=0.014). Similarly, NO and ADMA levels in the patients with migraine in the interictal period were found to be significantly higher as compared to control group (p=0.011, p=0.003). In conclusion, higher ADMA and NO levels of patients with migraine supported that oxidative stress and endothelial dysfunction may have a role in migraine pathogenesis.

Apolipoprotein E genotype in patients with cerebrovascular diseases and its effect on the disease outcome.

A total of 100 hospitalized stroke patients and 30 healthy controls were included in a study aiming to determine the predictive role of ApoE genotype polymorphism for stroke outcome in the Turkish population. The most frequent ApoE genotype was epsilon3/3 reflecting Asian population polymorphic distribution. ApoE polymorphism in the Eastern Turkish population was found to be independent of stroke type, OSCP subtypes of infarction, localization of hemorrhage, severity of carotid artery stenosis, and resultant stroke outcome. Distinct polymorphic results in populations from nearby regions suggest a multifactorial pathogenesis and presence of very complex genetic factors in the development of stroke and stroke outcome.

Association of apolipoprotein E genotype and cerebrovascular disease risk factors in a Turkish population.

The purpose of the present study was to investigate the predictive role of apolipoprotein E genotypes for stroke-related risk factors in the Turkish population. Among 100 stroke patients and 30 healthy subjects included in the study, most frequent Apo E genotype was epsilon3/3, compatible with polymorphic distribution of Asian population. VLDL and triglyceride levels in epsilon2/4(+) subjects were higher than in epsilon2/4(-) patients. HDL and homocysteine levels were higher in epsilon4/4 (+) subjects than in epsilon4/4 (-) stroke patients. These results suggest that ApoE polymorphism in this population was not associated with any other demographic or clinical variables except for lipid profiles and homocysteine levels.

The effect of venlafaxine HCl on painful peripheral diabetic neuropathy in patients with type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to evaluate the efficacy of venlafaxine HCl in the symptomatic treatment of painful peripheral diabetic neuropathy (PPDN) among patients with type 2 diabetes mellitus (DM). DESIGN: This study was designed as a prospective, randomized, and controlled trial. SETTING: This study was conducted at the Dicle University Medical Faculty (Diyarbakir, Turkey). PATIENTS: Sixty type 2 DM outpatients (47 females and 13 males) with PPDN who had a minimum visual analog scale (VAS) score of 40 mm were enrolled in this study. INTERVENTIONS: Patients randomized to the treatment group (n=30) received venlafaxine HCl, whereas those randomized to the control group (n=30) received a combination of vitamins B(1)and B(6) tablets. MEASURES: Severity of pain was measured by VAS, Short-Form McGill Pain Questionnaire, and numerical analog scale scores at admission and at the second, fourth, and eighth weeks of the study. Polyneuropathy was supported by electromyelography. OUTCOME: In the treatment group, severity of pain was measured as 70.0+/-13.0 in the VAS, as 24.9+/-6.2 in the Short-Form McGill Pain Questionnaire, and as 7.2+/-1.1 in the numerical analog scale. In the control group, it was measured as 73.0+/-8.0 in the VAS, as 26.8+/-6.2 in the Short-Form McGill Pain Questionnaire, and as 7.4+/-0.8 in the numerical analog scale (P>.05). RESULTS: The most common form of PPDN was distal symmetrical sensorimotor polyneuropathy in both groups (46.8% vs. 50.0%). At the end of the study, there was a significant difference in severity of pain between the groups. In the treatment group, scores were 8.5+/-5.2 and 3.1+/-1.6 in the Short-Form McGill Pain Questionnaire and numerical analog scale, respectively; in the control group, these were 20.5+/-7.0 and 5.5+/-1.6, respectively (P<.001). CONCLUSIONS: Venlafaxine HCl is a safe and well-tolerable analgesic drug in the symptomatic treatment of PPDN; however, it has minimal adverse effects. It showed its efficacy markedly in the second week of therapy.

[The prevalence of dementia three months after stroke and its risk factors]. / Inme sonrasi demans: sikligi ve risk faktörleri.

OBJECTIVE: The aim of this study was to determine the prevalence of post-stroke dementia (PSD) and its possible clinical and sociodemographic risk factors 3 months after the index stroke episode. METHODS: Among 147 patients who were hospitalized in the inpatient neurology clinic of Dicle University Faculty of Medicine with a diagnosis of stroke, 106 that met the inclusion criteria were included in the study 3 months after the index stroke. All patients underwent a detailed systemic and neurological examination, as well as a clinical interview in an effort to determine the sociodemographic features, and both vascular and non-vascular risk factors of stroke. Routine laboratory examinations and cranial imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) were also conducted. The functional, clinical, and cognitive status of the patients were evaluated at the time of hospitalization and 3 months later with the Barthel Index, NIH Stroke Scale (NIHSS), and Mini Mental State Examination (MMSE), respectively. RESULTS: Of the 106 patients included in the study, 32 (30.2%) were diagnosed with PSD. Multivariate analyses revealed that increased age, presence of atrial fibrillation, multiple brain lesions, and cognitive and functional status during hospitalization predicted the development of PSD in this group of patients. CONCLUSION: The results corroborate previous findings that PSD is a common complication of stroke. Early recognition and treatment of PSD risk factors will definitely diminish the burden of stroke on society and help to improve patient quality of life.

Cervical intramedullary granuloma of Brucella: a case report and review of the literature.

The aim of this study was to present a unique case of intramedullary brucellar granuloma (IBG) and to discuss the diagnosis and management. To our knowledge, only one case of thoracic IBG has been reported previously, and our case is the first in cervical spine. A 35-year-old female patient was admitted with headache, pain and weakness in her four extremities. She had no gastrointestinal symptoms and fever. She had been diagnosed with Brucella meningitis 3 months ago and a triple therapy of doxycyclin, rifampicin and trimetoprim/sulfametoxazol (TMP/SMZ) had been started. Medical history revealed that she had ingested raw cheese and taken her medication improperly. Loss of strength was detected in her four extremities, which led us to assume the formation of a mass lesion at cervical level. Therefore, we performed a magnetic resonance imaging scan and found enhancement of an intramedullary mass lesion at cervical 1-2 level. Diagnosis of neurobrucellosis was confirmed by titer of >1/160 Brucella antibodies both in blood and cerebrospinal fluid. Based on these findings, brucellar granuloma of cervical spine was diagnosed and a combination therapy of doxycyclin, TMP/SMZ and rifampicin was administered for additional 6 months. At the ninth month of treatment, the patient recovered both radiologically and clinically. Our case is unique, in terms of cervical IBG formation. The excellent response to antimicrobial therapy in our patient suggests that, a trial of medical treatment for 6 months may be effective in such cases.

Angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms in children with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a progressive, debilitating, and fatal brain disorder caused by mutant measles virus infection. Although both viral and host factors seem to be involved in SSPE, the exact pathogenesis remains to be determined. Autoimmune demyelination is characteristic of SSPE. The blood angiotensin-converting enzyme (ACE) activity and angiotensin II (Ang II) levels are associated with the ACE gene polymorphism. Proinflammatory effects of Ang II may contribute to the development of SSPE. The aim of this study was to investigate whether the ACE and Ang II type 1 receptor (AT1R) (A1166C) gene polymorphisms were associated with SSPE. The polymorphisms were investigated by polymerase chain reaction (PCR) in 43 patients with SSPE and 100 healthy controls. The genotype distribution of the SSPE children and healthy controls were as follows: DD 58.1% versus 34.0, ID 37.2% versus 48.0%, and II 4.7% versus 18.0, respectively (P = 0.012). Allele frequencies of patients and controls were D 76.7% versus 58.0%, and I 23.3% versus 42.0%, respectively (P = 0.004). The frequency of DD genotype and D allele were significantly higher in SSPE children compared with controls (P < 0.05). AT1R gene polymorphism distribution was found to be similar in SSPE children and control subjects: AA 55.8% versus 60.7%, AC 37.2% versus 32.1%, and CC 7.0% versus 7.2%, respectively (P > 0.05). In conclusion, the results of this study suggest that the DD genotype of ACE I/D polymorphism may be related to SSPE. Due to small size of this study, further studies with more patients are needed to confirm these results.

Economic impact of primary headaches in Turkey: a university hospital based study: part II.

This study was planned to investigate the economic impact of headache on Turkish headache sufferers attending a tertiary care outpatient headache clinic.A total of 937 headache patients were included in this study and questioned using a questionnaire for the profile of patients and headache, quality of life of patients and economic impact of headache. The median total direct cost was found to be 88.0 USD and the median total cost was 160.7 USD. The drug treatment cost was the highest item followed by the specialist outpatient care cost. The average lost and inefficient work/school days was 1.5 (0-45) and 8.4 (0-100) days for one year. It was shown that loss of productivity was higher for migraine without aura group when compared with the episodic and chronic tension-type headache groups. The results of this nationwide university hospital based study methshowed that headache, especially migraine, has considerable economic impact on patients.