The probable role of insulin resistance and SIRT1 proteins in the Alzheimer's disease.

OBJECTIVE: Recent evidence suggests that insulin resistance may play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, the probable role of insulin resistance in the pathogenesis of AD was investigated in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: Serum amyloid beta (Aß) (1-42), insulin like growth factor-1 (IGF-1), sirtuin1 (SIRT1) and leptin protein levels were measured in serum samples of control (n = 26), probable AD (n = 26), and probable AD+T2DM patients (n = 12) using ELISA method. Mini mental state examination (MMSE) was performed to the patient and control groups. RESULT: Serum IGF-1 significantly increased in the probable AD+T2DM group as compared to the control and probable AD groups (p ˂ 0.05). The levels of serum leptin significantly decreased in the probable AD and AD+T2DM groups as compared to the control (p ˂ 0.05). There were no statistically significant differences in serum Aß (1-42) and SIRT1 levels among groups (p > 0.05). CONCLUSION: The significant decrease in serum leptin levels in AD patients may indicate that it may be a therapeutic marker in AD. The level of serum Aß peptide and SIRT1 proteins can vary depending on the stage of the disease. Therefore, this study should be supported by more comprehensive studies in terms of the number of patients in advanced stage (Tab. 1, Fig. 4, Ref. 29).

Cerebral blood flow velocity in migraine and chronic tension-type headache patients.

INTRODUCTION: The present study seeks to use transcranial Doppler ultrasound to evaluate cerebral blood flow velocities in anterior and posterior circulation arteries, during an attack-free episode in migraine patients, with and without aura, as well as in chronic tension-type headache patients who were not receiving prophylactic medication. METHODS: A total of 50 patients (35 female, 15 male) were evaluated during a headache-free episode: 30 migraine patients without aura (mean age: 32±8 years), 10 migraine patients with aura (mean age: 34±4 years), and 10 patients with chronic tension-type headache (mean age: 34±5 years). RESULTS: No significant difference was present between anterior, middle, and posterior cerebral and vertebral arteries' blood flow velocities between migraine patients, with and without aura, or in patients with a tension-type headache, and normal controls (p>0.05). However, a significant increase in basilar artery cerebral blood flow velocities relative to controls was present in patients with a tension-type headache (p>0.001). CONCLUSION: It is difficult to predict the main reason for the significant increase in basilar artery blood flow velocities in patients with chronic tension-type headache. It may be due to constriction of conductance or the dilatation of the resistance vessels.

Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis.

BACKGROUND: Suppressors of cytokine signaling (SOCS) and brain-derived neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors for MS pathogenesis. The impact of exercise on these factors is yet to be fully elucidated in patients with MS. OBJECTIVE: The primary aim of this study is to investigate the effect of 8-week combined exercise training on serum concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the effects of combined exercise training on balance, functional exercise capacity, and fatigue in patients with MS. METHODS: Serum SOCS1, SOCS3, and BDNF levels were assessed in 36 MS patients and 18 healthy individuals. In addition, balance, functional exercise capacity, and fatigue were assessed in the patients with MS. The patients were randomly divided into the combined exercise group (MS-EX, n:18) and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise training. RESULTS: The serum SOCS1, SOCS3, and BDNF levels were similar in the MS patients and healthy control (HC). In MS-EX, the serum BDNF level, balance, functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but serum SOCS3, BDNF, balance and functional exercise capacity did not change (p>0.05). CONCLUSIONS: In summary, the combined exercise training improved BDNF, and physical performance in patients with MS. But, future studies are needed to clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise on SOCS.

The effects of Mat Pilates and Reformer Pilates in patients with Multiple Sclerosis: A randomized controlled study.

BACKGROUND: Pilates is an exercise method which increases strength and endurance of core muscles and improves flexibility, dynamic postural control and balance. OBJECTIVE: To analyze and compare the effects of Mat and Reformer Pilates methods in Patients with Multiple Sclerosis (MS). METHODS: Thirty-eight patients with MS were included in the study. Participants were randomly divided into 3 groups as Mat Pilates, Reformer Pilates and control groups. The subjects in the Pilates groups did Mat or Reformer Pilates for 8 weeks, 2 days a week. The control group did breathing and relaxation exercises at home. Balance, functional mobility, core stability, fatigue severity and quality of life were evaluated. RESULTS: Balance, functional mobility, core stability, fatigue severity and quality of life improved after Pilates in Mat and Reformer Pilates groups (p < 0.05). On the other hand, we could not find any changing in the control group (p > 0.05). When the gain obtained in the Pilates groups is compared, it has been observed that progress has been more in trunk flexor muscle strength in the Reformer Pilates group (p < 0.05) and that the gain has been similar in the other parameters (p > 0.05). CONCLUSIONS: As a result, patients with MS have seen similar benefits in Reformer Pilates and Mat Pilates methods.

Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters.

PURPOSE: To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. METHODS: This is an observational case-control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation test. RESULTS: The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. CONCLUSIONS: In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found.

Heparin-induced thrombocytopenia leading to stroke, lower extremity arterial occlusive disease, and skin necrosis: a case report.

Enoxaparin sodium is a low molecular weight heparin (LMWH) used to treat and prevent deep venous thrombosis (DVT). The common complications related to the use of heparin are bleeding, allergic reaction, and osteoporosis. A less common complications are thrombocytopenia and thromboembolism that may not be generally recognized. We present a case of low molecular weight (LMW) heparin-induced thrombocytopenia (HIT) causing stroke, lower extremity arterial occlusion, and skin necrosis. Monitoring the platelet count is essential for early diagnosis of HIT. All patients who undergo heparinization should have a baseline platelet count done before the regimen is started and should be monitored closely especially during the first weeks of treatment.

Iron-Deficiency Anemia Leading to Transient Ischemic Attacks due to Intraluminal Carotid Artery Thrombus.

Reactive thrombocytosis secondary to iron-deficiency anemia (IDA) is a rare but recognized cause of stroke. We report the case of a patient with iron-deficiency anemia presenting with multiple transient ischemic attacks (TIA) due to intraluminal thrombus of an internal carotid artery. The putative mechanisms underlying anemia and stroke syndromes are not completely understood, and it is believed that iron deficiency may cause ischemic stroke by several potential mechanisms. Thrombocytosis is often associated with iron deficiency, and microcytosis produces a reduction in the red cell deformability and could produce a hypercoagulable state. The platelet count and function observed in iron-deficiency anemia could act synergistically to promote thrombus formation, especially in the setting of an underlying atherosclerotic disease. The presence of floating thrombus in a patient with clinical and MRI evidence of stroke represents a significant therapeutic dilemma and requires immediate decision about treatment.

A case of multiple sclerosis and celiac disease.

Objectives. Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS). Since a correlation between gluten intake and incidence of MS had been reported, the relationship of antigliadin antibodies and MS was debated. Case Report. We report the case of a 45-year-old female MS patient who is under interferon treatment. After seven years of monitoring, during her routine gastroenterological assessment, she was diagnosed with celiac disease. Conclusion. Beside the neurological manifestations that have been demonstrated in about 10% of celiac disease (CD) patients, white-matter abnormalities in brain MRI are uncommon and controversial. But in the literature, MS seems to be associated with CD as in our patient. We suggest that MS patients with gastroenterological complaints should undergo an assessment for CD.

Event related potentials in children of alcoholics.

Assessment of ERPs (Event Related Potentials) is a special area of interest in research on vulnerability to alcoholism in human subjects. ERP not only provide information about potential neurofunctional anomalies in healthy individuals, but also relate those neurofunctional characteristics to the cognitive process involved. The aim of the present study is to evaluate the effects of chronic alcoholism and alcoholism risk on children of alcoholic fathers by using ERP parameters. 24 children of alcoholic fathers (9 boys, 15 girls) with a mean age of 18 +/- 3 (range: 15-25) and 17 control subjects (children of non-alcoholic fathers with out a family history of alcoholism) were included to the study. The age range was from 15 to 25 (mean: 21 +/- 3). N200 potential latency recorded from the parietal electrode position was significantly prolonged (p = 0.032) and amplitudes of P200 potential also recorded from the parietal region was significantly low (p = 0.043) relative to controls. However, the rest of the event-related potential parameters including P300 latency and amplitudes recorded from FZ, CZ, PZ electrode positions did not differ significantly from the children of non-alcoholic fathers. The difference in our results from the previous studies may be due to various factors. Genetic, gender, environmental, educational and social factors may have an overall effect on ERP and we believe these factors may be the cause of the differences seen in our study when compared to the previous ones. We believe the gender differences in our group may have had effected the overall results. Consecutive studies with more subject participation are needed to confirm and settle this issue.

SSR abnormalities in chronic alcoholics.

We performed sympathetic skin response (SSR) studies on 29 male patients diagnosed as chronic alcoholics according to DSM-IV criteria. The average age was 43 years and the mean duration of alcohol abuse was 21 years, with all patients having a history of alcohol abuse for a minimum of 4 years. None of the patients had any symptoms and/nor signs related to autonomic nervous system dysfunction and all demonstrated normal nerve conduction velocities. Hand and foot latencies in alcoholics were prolonged relative to controls and the difference was statistically significant: reflected by p values of 0.02 and 0.004, respectively. Forty-four percent of patients demonstrated abnormal results. The unilateral prolongation of the lower extremity latency was the most commonly found abnormality (24%). Finding abnormal SSR in this patient population has made us aware that SSR has the potential to detect subclinical autonomic nervous system dysfunction even in patients who do not have autonomic complaints or neuropathy and to provide information about a part of the peripheral nervous system small unmyelinated C fibers that can not be assessed by currently performed techniques used in clinical EMG laboratories or by physical examination.

Blink reflex abnormalities in chronic alcoholics.

PURPOSE: The aim of the present study was to evaluate the efficacy of blink reflex as a method for obtaining early diagnosis of cranial nerve involvement in alcoholic patients. MATERIALS AND METHODS: The study was conducted on 30 male alcoholics with a mean age of 43 years. They had histories of alcohol abuse for at least 6 years (mean: 25). At the time of recording, they had undergone detoxification treatment for a mean of 27 days. RESULTS: R1 (early response), R2Y (second ipsilateral response), and R2C (second contralateral response) latencies in alcoholics were prolonged relative to controls and the differences were statistically significant (p < 0.02, p < 0.001, p < 0.001, respectively). According to the defined criteria, 40% of the patients had abnormal responses, and the most common abnormality was the unilateral prolongation of R1 (13%). CONCLUSION: Finding abnormal blink reflex responses in alcoholic patients has suggested that blink reflex testing is a useful method for the evaluation of subclinical cranial nerve involvement in alcoholic patients. Blink reflex testing may be useful in detecting early changes and in the follow-up of alcoholic disorder.

The role of qualitative and quantitative MRI assessment of multiple sclerosis lesions according to their in evaluating the efficacy of intravenous immunoglobulin G.

We evaluation of the role of determining the distribution of brain-stem, cerebellar and cerebral lesions in number and volume by MRI in determining the efficiency of treatment of multiple sclerosis (MS). We studied 24 patients diagnosed as having relapsing and remitting MS, of whom 12 received intravenous immunoglobulin G; a control group of 12 were given placebo. In a double-blind study, MRI was obtained initially and at 3, 6 and 9 months, and interpreted without knowledge of clinical findings, laboratory tests or treatment. The lesions were classified according to their distribution and evaluated qualitatively and quantitatively. Each patient was also examined clinically and scored according to the expanded disability status scale (EDSS) following every MRI examination. All patients in the treatment group showed significant improvement. The lesions decreased in both in size and number in all sites. In the control group lesions increased both in number and size in all sites, but only the increase between 3()and 6 months was statistically significant. In both groups, significant apparent changes were detected in the cerebellum and brain stem. Volumetric evaluation was found to be more helpful than qualitative assessment.

The roles of blink reflex and sympathetic skin response in multiple sclerosis diagnosis.

The neurological history and examination are important in multiple sclerosis (MS) diagnosis, but early and accurate diagnosis of MS often requires judicious use of paraclinical information. Electrophysiologic techniques have an important role in demonstrating lesions that are clincally silent but magnetic resonance imaging (MRI) is accepted as the most sensitive paraclincal test for detecting asymptomatic dissemination in space for MS patients. In order to test the sensitivity of electrophysiologic techniques in diagnosing asymptomatic MS lesions, we performed blink reflex (BR) and sympathetic skin response (SSR) studies on 13 female (mean age 39 -/+ 9 years) and 8 male (mean age 35 -/+ 14 years) patients with a diagnosis of definite MS who do not have any clinical symptoms nor signs referable to brainstem or autonomic system dysfunction. Forty three percent of patients on SSR testing and 40% of patients on BR testing demonstrated abnormal results. In countries with unfavorable economic conditions, diagnosis, especially the follow-up evaluation of MS patients, poses a major dilemma. The role of diagnostic techniques in MS diagnosis when MRI is available is an economic problem. Diagnostic evaluation adds to the cost of health expenses. We usually choose to perform MRI only at the initial diagnosis of MS and perform follow-up evaluations during remissions and exacerbations with the aid of electrophysiologic techniques. We stress the importance of electrophysiologic screenings in MS patients because they provide data that cannot be obtained through clinical evaluations only with a little cost.

Serum nitric oxide metabolites in patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by myelin breakdown. The free radical nitric oxide (NO), which is considered to be a major metabolite in immune function and in autoimmune disorders, is among the possible mediators causing the inflammatory reactions in MS. Consequently, NO has been implicated in the pathogenesis of MS and its animal model experimental allergic encephalomyelitis (EAE). In this study, stable metabolites of NO (NO(2-)+NO(3-)) levels were determined in sera of MS patients (n=23) and control subjects (n=16). NO(2-)+NO(3-) levels were higher in MS patients when compared to control subjects. However, there was not any correlation with serum NO(2-)+NO(3-) values and clinical features of the disease such as duration of sickness, the time elapsed from the last attack and EDSS values. Our results imply that nitric oxide may be involved in the pathogenesis of MS although further studies are required to elucidate underlying mechanisms.

Sympathetic skin response in diabetic neuropathy.

Autonomic neuropathy is a complication of diabetes mellitus (DM) in substantial proportion of cases and may cause definite autonomic symptoms. Because conventional electrophysiological methods do not assess the autonomic nervous system, simple reproducible tests were developed. One of them is sympathetic skin response (SSR) which provides useful information about the status of sympathetic postganglionic function. The aim of this study is to perform SSR in diabetic patients to see whether this test can be used as an electrophysiological method for the diagnosis and confirmation of diabetic autonomic neuropathy. 20 diabetic patients who had electrophysiologically confirmed polyneuropathy but showed no symptoms or signs referable to autonomic system dysfunction were included. 14 (70%) patients demonstrated abnormal SSR. 2 abnormal patterns were observed. An absent response in at least one tested lower extremity (50%) and prolonged foot with normal hand latency (20%). 6 patients (30%) demonstrated no abnormalities. Foot and hand latencies in diabetics did not differ significantly from those of normal controls (p: 0.4, p: 0.1) and no correlation could be found with latencies and duration of sickness, patient's age and HbA1c values. We believe latency measurement is an objective measure of conduction in multineural pathways and can detect subclinical involvement of sympathetic nervous system in diabetics who do not manifest symptoms or signs referable to autonomic system dysfunction.

Pattern visual evoked potential (PVEP) evaluation in hypothyroidism.

Dysfunction of the central nervous system (CNS) is an important consequence of thyroid hormone deficiency. Evoked potentials like visual evoked potentials (VEP) provide a reliable and objective measure of function in related sensory system and tracts. In this study pattern-shift VEP (PVEP) recordings were performed on 48 newly diagnosed hypothyroid patients. Twenty-four had sub-clinical and 24 had overt hypothyroidism. None of the patients had clinical symptoms or signs referable to CNS dysfunction. Their mean age was 44+/-12 yr. The response to pattern stimulation on the normal control subjects was a triphasic response with a prominent positive wave (P100) with a peak latency of 84-105 (mean: 96+/-4) milliseconds (ms). In patients with hypothyroidism mean P100 latency was (mean: 97+/-6) ms and the difference between the 2 groups was not statistically significant. (p>0.05) Delays above the average latency +/-2.5 SD of the mean of the control subjects was defined as a criteria for an abnormality. According to defined criteria 6 (12.5%) patients demonstrated abnormal PVEP at least on one tested side. Previous studies conducted on small patient populations stated there is high percentage of VEP abnormalities in hypothyroid patients. However, this fact was not confirmed by our study. We believe abnormalities of PVEP will be more prominent in untreated patients in the advanced stage of the disease, or in patients who have a neurological involvement; such as apathy, impaired memory or cerebellar dysfunction. Consecutive studies, in a more clearly defined and selected patient population, are needed to confirm and settle this issue.

Blink reflex abnormalities in diabetes mellitus.

BACKGROUND: Damage of the peripheral nervous system is particularly frequent in diabetes mellitus (DM), but somatic cranial neuropathies usually presenting as mononeuropathies are rare. Oculomotor and facial nerves are among the most commonly affected, whereas the Vth, IXth and Xth cranial nerves are less often affected. While existing neurophysiological tests in the subclinical diagnosis of damage to the peripheral nerve in diabetic patients have advanced, the same does not hold true for the subclinical diagnosis of the central nervous system (CNS). Electrophysiological studies such as the blink reflex was shown to be an effective method for revealing subclinical involvement of cranial nerves in generalised neuropathies. The aim of the present study was to evaluate the efficacy of blink reflex as a method for obtaining early diagnosis of cranial nerve involvement in diabetic patients frequently affected with peripheral neuropathy. METHODS: Twenty diabetic patients with electrophysiologically confirmed neuropathy were included in the present study for the evaluation of blink reflex. Patients with earlier cranial nerve involvement were excluded. RESULTS: Abnormal blink reflex responses were found in 55% of patients studied. R2Y and R2C latencies in diabetic patients were prolonged relative to controls (p<0.001 and p<0.001, respectively). However R1 values in diabetic patients did not differ significantly from those of normal controls (p<0.5). R2Y and R2C prolongation showed a positive correlation with the duration of disease (p=0.015 and p=0.009, respectively). However the same correlation could not be found with R1 values. No correlations were found between R1, R2Y, R2C values and HbA(1c) nor between R1, R2Y, R2C values and patients' age. CONCLUSION: We suggest that blink reflex testing is a useful method for obtaining early diagnosis of cranial nerve compromise in diabetic patients who do not show any clinical symptoms or signs of CNS involvement.

Current literature in diabetes.

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Prediction; 7 Prevention; 8 INTERVENTION: a&rpar General; b&rpar Pharmacology; 9 Pathology: a&rpar General; b&rpar Cardiovascular; c&rpar Neurological; d&rpar Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13 Techniques. Within each section, articles are listed in alphabetical order with respect to author (9 Weeks journals - Search completed at 1st Aug 2001)

The correlation between cerebrospinal fluid findings and evoked potentials during an acute MS attack.

Clinically definite Multiple Sclerosis (MS) cases have an index greater than 0.7. Evoked potentials using geometrical patterns and click stimuli respectively and electrical stimulation of mixed nerve trunks evokes low level electrical impulses along a nerve. Prolonged latencies and changes in amplitude in these evoked potentials are thought to reflect sensory loss. This study is performed to determine whether there is a correlation between cerebrospinal fluid (CSF) findings and evoked potentials in MS during an acute MS attack. 10 male and 10 female patients' (20-55) mean (37.75) were included in to the study. They were diagnosed as definite MS with their clinical and MRI findings. During the acute attack 10 (50%) patients out of 20 had high Ig G index and one (10%) had oligoclonal band positivity. Of these 10 patients 8 (4 M, 4 F) had pathology in their evoked potentials while two had normal evoked potential findings. 8 of (80%) 10 patients whom had normal Ig G index during the acute attack had evoked potential pathology while (20%) had normal Ig G index and evoked potentials during the acute attack. Of the 8 patients which had high Ig G index and pathological evoked potential findings during acute attack were evaluated. VEP, BAEP latencies were found to be prolonged as Ig G index increased. (p < 0.05) However the same correlation can not be found with SEP parameters.