Ischemic stroke mimics: A comprehensive review.

BACKGROUND: Ischemic stroke is the leading cause of disability and one of the leading causes of death. Ischemic stroke mimics (SMs) can account for a noteble number of diagnosed acute strokes and even can be thrombolyzed. METHODS: The aim of our comprehensive review was to summarize the findings of different studies focusing on the prevalence, type, risk factors, presenting symptoms, and outcome of SMs in stroke/thrombolysis situations. RESULTS: Overall, 61 studies were selected with 62.664 participants. Ischemic stroke mimic rate was 24.8% (15044/60703). Most common types included peripheral vestibular dysfunction in 23.2%, toxic/metabolic in 13.2%, seizure in 13%, functional disorder in 9.7% and migraine in 7.76%. Ischemic stroke mimic have less vascular risk factors, younger age, female predominance, lower (nearly normal) blood pressure, no or less severe symptoms compared to ischemic stroke patients (p < 0.05 in all cases). 61.7% of ischemic stroke patients were thrombolysed vs. 26.3% among SMs (p < 0.001). (p < 0.001). Overall intracranial hemorrhage was reported in 9.4% of stroke vs. 0.7% in SM patients (p < 0.001). Death occurred in 11.3% of stroke vs 1.9% of SM patients (p < 0.001). Excellent outcome was (mRS 0-1) was reported in 41.8% ischemic stroke patients vs. 68.9% SMs (p < 0.001). Apart from HINTS manouvre or Hoover sign there is no specific method in the identification of mimics. MRI DWI or perfusion imaging have a role in the setup of differential diagnosis, but merit further investigation. CONCLUSION: Our article is among the first complex reviews focusing on ischemic stroke mimics. Although it underscores the safety of thrombolysis in this situation, but also draws attention to the need of patient evaluation by physicians experienced in the diagnosis of both ischemic stroke and SMs, especially in vertigo, headache, seizure and conversional disorders.

Prevalence and Risk Factors of Internet Addiction among Hungarian High School Teachers.

The extensive availability of internet has led to the the recognition of problematic internet use (so called internet addiction, IA) mostly involving adolescents. There is limited data about the prevalence of IA in adults. Here we present a study focusing on the prevalence and risk factors of internet addiction among high school teachers. Overall 2500 paper-based questionnaires were successfully delivered and 1817 responses received (response rate of 72.7%). In our study 1194 females (65.7%) and 623 males (34.3%) participated. In a multivariate analysis including of all factors (demographic data, internet habits, comorbidity etc.) age <35 years (OR: 6.098, CI: 5.09-7.08, p < 0.001), male gender (OR = 5.413, CI: 4.39-6.18, p = 0.002), surfing on the internet > 5 h daily (OR 2.568, CI: 2.03-3.39, p < 0.001), having no children (OR: 1.353, CI: 1.13-1.99, p = 0.0248), and having secondary employment (OR = 11.377, CI: 8.67-13.07, p = 0.001) were significantly associated with internet addiction. This is the first study from Hungary showing the prevalence and risk factors of internet addiction among high school teachers. A small, but significant proportion suffered from IA. Our study also draws attention to the risk factors of IA such as younger age, family status and working type.

Neuropathic Low Back Pain and Burnout among Hungarian Workers.

Burnout is an increasingly prevalent syndrome mainly involving those working in human services. Although it is categorized as an occupational phenomenon and not as a medical condition, it seems to be strongly associated with several diseases such as pain syndromes. However, no studies examined the association between neuropathic low back pain and burnout. This questionnaire-based study was carried out between April 2019 and March 2020 in three main sites among teachers, social workers and healthcare workers. Demographic criteria included age, gender, marital status, number of children, type of work, years spent with work, work schedule, legal relation, secondary employment. Included diseases were diabetes, hypertension, ischemic heart disease, generalized pain (pain involving more than one area of the body) and depression. Low back pain was assessed by the painDETECT questionnaire, burnout was measured with the Maslach Burnout Inventory (MBI) and depression was measured by the Beck Depression Inventory. Dysfunctional attitudes were also recorded. Overall, 1500 questionnaires were successfully delivered and 1141 responses received (response rate of 76%). Three hundred social workers, 399 teachers, 339 paramedics, 35 doctors and 68 medical attendants have completed our survey. In a multivariate analysis including of all factors (demographic criteria, burnout, depression, dysfunctional attitudes, comorbidity etc.) neuropathic low back pain was associated with age > 62 (OR = 3.981, p = 0.01), number of children ≥ 2 (OR = 2.638, p = 0.003), job type (being a social worker) (OR = 6.654, p < 0.001), burnout (OR = 2.577, p < 0.001), current depression (OR = 2.397, p < 0.001), and suffering from generalized pain (OR= 4.076, p < 0.001). This is the first study showing the association of burnout and neuropathic low back pain, which is the most common cause of disability. Based on our results neuropathic low back pain and burnout have similar risk factors and consequences which raises the possibility of similar pathophysiology.

Internet Addiction and Burnout in A Single Hospital: Is There Any Association?

The extensive availability of the internet has led to the recognition of problematic internet use, the so-called Internet Addiction (IA), mostly involving adolescents. Burnout can lead to substance abuse or addictive behaviour (such as internet addiction) as a coping method. There are insufficient data about internet addiction and its possible association with burnout in adults, especially among healthcare workers. The aim of our present study was to focus on prevalence and the risk factors of internet addiction and its possible association with burnout among healthcare workers in a single hospital applying a questionnaire-based survey. In total, 49 doctors (10.1%), 198 nurses (40.9%), 123 medical assistant (25.4%), 73 other healthcare workers (15.1%), and 42 (1.7%) healthcare associated workers (cleaning, laundry, etc.) have completed our survey. In a multivariate analysis, IA was associated with age between 18 and 25 (OR: 2.6, p = 0.024), surfing on the internet >5 h daily (OR 25.583, p < 0.001), being single (OR: 4.275, p = 0.006), being childless (OR: 3.81, p = 0.011), working less than five years (OR 2.135, p = 0.048) and job type (being healthcare associated worker, OR: 2.907, p = 0.009). Illicit drug intake (OR 52.494, p < 0.001), and diabetes (OR: 4.122, p = 0.043) were also significantly associated with internet addiction. No association of burnout and IA could be found. A small but significant proportion of our healthcare workers suffered from IA, which was associated with substance abuse and diabetes in multivariate analysis. Our study also draws attention to the risk factors of IA such as younger age, family status, working type and working hours internet use. The possible association of burnout and IA merits further investigation.

Associations between serum L-arginine and ficolins in the early phase of acute ischemic stroke - A pilot study.

INTRODUCTION: Activation of both the L-arginine and the lectin pathway contributes to the pathophysiology and the outcome of acute ischemic stroke (AIS). However, the interplay between the two systems has not yet been examined. METHODS: A total of 44 patients with AIS were recruited into this study. Serial measurement of serum L-arginine, asymmetric and symmetric dimethylarginine (ADMA, SDMA), and hsCRP, ficolin-2, ficolin-3, MAP-1, MASP-3 and mannose-binding lectin (MBL) were analyzed within 6 h after onset of stroke and 72 h later. Outcomes were assessed as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 h, poststroke infection, and death by 1 month. RESULTS: In the hyperacute stage of AIS, ficolin-3, MAP-1 and MBL were positively correlated with L-arginine within 6 h after onset of symptoms (p<0.05 respectively). Significantly lower ficolin-3 and MASP-3 levels were found at 72 h in patients, who developed post-stroke infection after day 4, when compared to patients without post-stroke infections (p=0.03 and p=0.009). At 72 hours, ficolin-3 levels negatively correlated with S100B (p=0.01). Ficolin-3 at 72 post-stroke hours remained an independent predictor of post-stroke infection, while only hsCRP was an independent predictor of 30-day mortality. CONCLUSION: Early consumption of ficolin-3 is associated with complications such as post-stroke infections. In the hyperacute phase of AIS, the positive correlation between ficolins and the NO donor L-arginine may reflect the protective role of L-arginine presumably by improving the cerebral microcirculation in a prothrombotic environment induced by complement activation.

Framingham Risk Stratification of Middle-Aged Migraineurs.

Introduction. Migraine is a common primary headache disorder involving about 10-15% of the whole population. Several epidemiological and prospective studies showed a link between migraine (especially migraine with aura) and cardio- and cerebrovascular events. OBJECTIVES: We prospectively analyzed the data of vascular event-free middle-aged patients with migraine who were referred to our Headache Clinic between 01/2014 and 01/2018. Framingham 10-year risk were calculated; covariates included in the analysis were age, total cholesterol, HDL cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, and diabetes status. RESULTS: Total of 1037 patients were screened and 221 were selected, 161 were women (mean age 55.5 ± 5.2 years) and 60 were men (mean age 56 ± 6 years). 25 patients (11.3%) were labelled as having low risk, 162 patients (73.3%) had moderate risk, and 34 patients (15.4%) had high or very high risk. Blood pressure and lipid targets were reached in 73% and in 49% in the moderate risk and in 53% and 12% in the high risk/very high risk groups, respectively. Migraine with aura (MA) was associated significantly higher cardiovascular risk profile compared with migraine without aura (MO). About one-third of our nondiabetic patients had fasting blood glucose above the normal levels. 24 patients (mean age 60 ± 4.9 years) were diabetic. Mean blood pressure was 149/85 Hgmm, mean choleterol was 5.11 mmol/l, and mean LDL was 2.93 mmol/l in this subgroup, respectively, which do not fall within the recommended targets. CONCLUSION: Our article draws attention to the higher cardiovascular risk profile of middle-aged migraineurs and highlights the deficiency of primary prevention. Pain physicians must be aware of the cardiovascular aspects of migraine and holistic approach is required instead of focusing only on pain and pain relief.

Characteristics of Patients Referred To A Specialized Headache Clinic.

Headache is a common problem with great effect both on the individual and on the society. Recent studies raised the possibility of increasing rate of specialty referrals, inappropiate treatment and advanced imaging for simple headache. The aim of our study was to analyze the characteritics of patients (including duration of symptoms, headache type, brain imaging, treatment) referred to our specialized headache clinic between 01/01/2014 and 01/01/2015 by their general practitioners and primary care neurologists due to chronic/treatment-resistant headache syndromes. 202 patients (mean age 53.6 ± 17.6 years) were evaluated in our clinic (102 females, mean age 50.14 ± 16.11 years and 100 males, mean age 57 ± 18.1 years). Migraine (84/202) and tension-type (76/202) were the most common syndromes. 202 plain brain CT, 60 contrast-enhanced CT and 128 MRI were carried out by their general practitioners or other healthcare professioners including neurologists before referral to our headache centre. Despite of extensive brain imaging appropiate treatment was started less than 1/3 of all patients and significant proportion received benzodiazepines or opioid therapy. Furthermore, more than 10% of referred patients presented with secondary headache including one meningitis. The management of headache is still a challenge for primary care physicians leading to medical overuse. Vast majority of our patients should not be referred to our specialized headache clinic as they had uncomplicated headache or other underlying conditions than pain.

Early seizures after ischemic stroke: focus on thrombolysis.

INTRODUCTION: Stroke is a significant underlying cause of epilepsy. Seizures due to ischemic stroke (IS) are generally categorized into early seizures (ESs) and late seizures (LSs). Seizures in thrombolysis situations may raise the possibility of other etiology than IS. AIM: We overtook a systematic review focusing on the pathogenesis, prevalence, risk factors, detection, management, and clinical outcome of ESs in IS and in stroke/thrombolysis situations. We also collected articles focusing on the association of recombinant tissue-type plasminogen activator (rt-PA) treatment and epileptic seizures. RESULTS: We have identified 37 studies with 36,775 participants. ES rate was 3.8% overall in patients with IS with geographical differences. Cortical involvement, severe stroke, hemorrhagic transformation, age (<65 years), large lesion, and atrial fibrillation were the most important risk factors. Sixty-one percent of ESs were partial and 39% were general. Status epilepticus (SE) occurred in 16.3%. 73.6% had an onset within 24 h and 40% may present at the onset of stroke syndrome. Based on EEG findings seizure-like activity could be detected only in approximately 18% of ES patients. MRI diffusion-weighted imaging and multimodal brain imaging may help in the differentiation of ischemia vs. seizure. There are no specific recommendations with regard to the treatment of ES. CONCLUSION: ESs are rare complications of acute stroke with substantial burden. A significant proportion can be presented at the onset of stroke requiring an extensive diagnostic workup.

[Chronic orofacial pain]. / Krónikus orofacialis fájdalmak.

Orofacial pain is the common name of a variety of disorders from inflammatory diseases to neuropathic pain syndromes. This condition is quite common, it may involve 7% of the whole population. Patients (and doctors) are not aware of the origin of their complaints, therefore initial management falls among the variety of healthcare professionals. The aim of our review was to summarize the current evidence of chronic orofacial pain including diagnosis, management and pitfalls. Orv Hetil. 2019; 160(27): 1047-1056.

Relationship between Cardiac Troponin and Thrombo-Inflammatory Molecules in Prediction of Outcome after Acute Ischemic Stroke.

BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after stroke. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, 24 hours later, and at discharge. RESULTS: Concentration of MCP-1 at 6 hours was higher in the serum of patients with worsened NIHSS by 24 hours (P = .009). Concentration of hs-cTnT at both 6 and 24 hours was higher, if NIHSS worsened by discharge (P = .026 and P = .001). A cutoff value for hs-cTnT measured at T24 greater than or equal to 9.4 predicted worsened NIHSS on discharge with a sensitivity of 81% and a specificity of 74% (area: .808, P = .002). Concentration of hs-cTnT at both 6 and 24 hours was also higher in nonsurvivors compared with survivors (P = .03, respectively), and correlated with (1) tPA levels at 6 hours (P = .001 and P = .002, respectively); (2) MCP-1 concentration at 6 hours (P = .01 and P = .015, respectively); and increased hsCRP levels at 72 hours (P = .01, respectively). Concentration of hs-cTnT at 24 hours was an independent predictor of worsened NIHSS at discharge (odds ratio: 1.58, 95% confidence interval: 1.063-2.370, P = .024). CONCLUSIONS: Elevated concentration of hs-cTnT measured 24 hours after AIS is an independent predictor of progressing neurologic deficit in patients without apparent myocardial damage, and also correlates with acute elevation of tPA and MCP-1.

Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke.

BACKGROUND: Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive and independent associations to outcome. METHODS: Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. RESULTS: Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most of these correlations disappeared by 72 poststroke hours. Correlation of MCP-1 with both ADMA and SDMA levels at 6 hours was associated with both NIHSS worsening and poststroke infections, respectively; sCD40L and SDMA correlation at 6 hours was also associated with NIHSS worsening. Negative correlation between P-selectin and L-arginine concentrations in the hyperacute phase was associated with NIHSS worsening. Strong negative correlation was found between IL-6 and L-arginine levels in the hyperacute phase in patients with poststroke infection. Only L-arginine and SDMA at 72 hours were independently associated with poststroke infection respectively. CONCLUSIONS: Concentration of L-arginine and ADMA/SDMA differentially correlates with thrombo-inflammation in the hyperacute phase of ischemic stroke. Such correlations are independently associated with poststroke infection but not with other outcomes.

Dynamic changes in sleep-related breathing abnormalities in bilateral paramedian mesencephalon and thalamus stroke: a follow-up case study.

BACKGROUND: Bilateral paramedian thalamic stroke is characterized by hypersomnia, vertical gaze palsy, amnestic alteration, and apathic state. Combined lesion of the paramedian thalamus and mesencephalon bilaterally is extremely rare. Little is known about the breathing disturbances of the particular region due to the lesion. The following describes the specific case of a woman, age 62, with bilateral paramedian thalamic and mesencephalic stroke. Initially, the patient's complaints exhibited altered vigilance and vertical gaze palsy. Notably, following the acute phase, fluctuating hypersomnia was detected. The MRI (brain) revealed an ischemic lesion in the medial part of the mesencephalon and paramedian thalamus, bilaterally. AIMS: The aim of the present study is to elucidate the involvement and characteristics of sleep-related breathing abnormalities in the clinical manifestation of the combined paramedian thalamic and mesencephalic stroke. METHODS: Polysomnographic recordings were accomplished seven times with 1-week interval between the consecutive recordings, toward investigating the early changes of sleep and sleep-related breathing abnormalities. RESULTS: Sleep structure examination featured a decrease in N3 and REM ratio and an increase in N1 and N2 ratio with minimal improvement during the recovery period. In contrast, significant changes were found in the breathing pattern: the initial central apnea dominance was followed by obstructive apneas with a gradual decrease of the total pathological respiratory events. CONCLUSION: In addition to the structural abnormality of the sleep regulating network, sleep-disordered breathing is another possible cause of hypersomnia in patients afflicted with the present localization of the lesion.

Early Dynamics of P-selectin and Interleukin 6 Predicts Outcomes in Ischemic Stroke.

BACKGROUND: Thromboinflammatory molecules connect the prothrombotic state, endothelial dysfunction, and systemic/local inflammation in the acute phase of ischemic stroke. METHODS: We prospectively investigated (1) serial changes in the levels of thromboinflammatory biomarkers in 76 patients with acute ischemic stroke (6, 24, and 72 hours after onset); (2) compared with 44 patients with asymptomatic severe (≥70%) carotid stenosis and 66 patients with Parkinson disease; and (3) we applied multiple regression methods, relating biological biomarkers combined with demographic data and comorbidities to poststroke infection, death, and functional outcome, and assessed the ability of the models to predict each outcome. RESULTS: Interleukin 6 (IL-6) levels and change of IL-6 concentrations by 72 hours correlated with the size of tissue damage indicated by S100B titers. Levels of IL-6 and P-selectin at 72 hours were higher in patients with large-artery versus lacunar stroke. High concentration of IL-6, monocyte chemotactic protein 1, and S100B at 6 hours were associated with poststroke infections; high concentration of IL-6, S100B, and high-sensitivity C-reactive protein (hsCRP) correlated with death. Change of P-selectin from 6 to 72 hours by 1 unit increased the incidence of poststroke infections with an odds ratio of 22.7; each 100 units of IL-6 at baseline increased the odds of death by 9‰, and at 72 hours, the odds of poststroke infections by 4‰. Each unit of baseline hsCRP elevated the odds of death by 7%. CONCLUSIONS: In regression models, in which biological, demographic, and comorbid factors were combined, those biological biomarkers predicted poor outcome with high accuracy, which were characterized by an increasing concentration by 72 hours. Two particular biomarkers emerged to predict outcomes besides hsCRP: early dynamic changes in the systemic levels of P-selectin and IL-6.

[Role of antihypertensive drugs in the treatment of migraine]. / Vérnyomáscsökkento szerek szerepe a migrén kezelésében.

The treatment of migraine depends on the frequency, severity and concomitant diseases. There are several specific drugs developed for migraine prevention in addition to the additive antimigraine effects of some other non-specific drugs. The aim of this literature-based review is to summarize the possible antimigraine properties of different antihypertensive agents (beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, etc.) focusing on the possible side effects (avoidance of beta blockers in the absence of heart disease, possible antiparkinson effect of calcium channel blockers, additive effect of drugs modifying the renin-angiotensin system activity, etc.). Current evidence supports the use of angiotensin converting enzyme inhibitors (mainly lisinopril) and angiotensin receptor blockers (mainly candesartan) for long-term migraine prevention and blood pressure control. Long-term beta-blocker treatment should be avoided in the absence of ischemic heart disease due to possible unfavourable cardiovascular effects.

[Clopidogrel resistance in cerebrovascular disease -- results of one-year follow-up]. / Clopidogrelrezisztencia vizsgálata cerebrovascularis betegségben -- egyéves utánkövetés.

INTRODUCTION: In an earlier study the authors reported short-term benefits of clopidogrel treatment in patients with cerebrovascular disease. AIM: The aim of the authors was to analyze findings during a 12-month follow-up period. METHOD: 100 patients with a history of acute stroke or transient ischaemic attack have been included in the study. The efficacy of the therapy was assessed 7 and 28 days as well as 3, 6 and 12 months after initiation of medical therapy. Patients were divided into two parts (clopidogrel responder and resistant) based on their initial laboratory findings. Risk profiles, medical therapy, laboratory parameters and vascular events were compared between the two patient groups. RESULTS: After 7 days of treatment, clopidogrel seemed to be ineffective in 11 patients (11%). Strong, clinically significant correlations were found among blood pressure values, blood glucose and lipid parameters, serum C-reactive protein levels and platelet aggregation levels. An aggressive secondary preventive therapy resulted in a decrease of clopidogrel resistance and improvement in laboratory parameters. Patients who were clopidogrel resistant at baseline had significantly higher rate of vascular events compared to those who were clopidogrel responders (18.1 vs. 4.5%, p<0.01), although clopidogrel resistance was not an independent risk factor of unfavourable vascular outcome using a multivariate analysis. No adverse events or hemorrhagic complications were observed. CONCLUSIONS: Clopidogrel resistance and unfavourable outcome seems to be associated with "classical" risk factors underlying the importance of aggressive secondary prevention.

The L-arginine pathway in acute ischemic stroke and severe carotid stenosis: temporal profiles and association with biomarkers and outcome.

BACKGROUND: Endothelial dysfunction is associated with increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) resulting in a decreased production of nitric oxide, which regulates the vascular tone. METHODS: Patients with acute ischemic stroke (AIS, n = 55) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring. RESULTS: Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting infarct size, positively correlated with the level of SDMA at 72 poststroke hours; changes in concentration of S100 B positively correlated with changes in the concentration of ADMA by 72 hours. Change in concentration of both ADMA and SDMA correlated with the change in concentration of hsCRP. Concentrations of L-arginine and hsCRP at 72 poststroke hours, respectively, were independent predictors of poststroke infection. S100 B level measured within 6 hours after the onset of AIS and hsCRP at 72 poststroke hours were independent predictors of death. CONCLUSIONS: Metabolites of the L-arginine pathway were elevated in the very acute phase of ischemic stroke indicating a more pronounced endothelial dysfunction compared with AsCS. An increased basal L-arginine level in patients with AIS might be an adaptive mechanism; such transient elevation of the L-arginine/ADMA ratio at 24 poststroke hours may suggest that a temporary increase of L-arginine along with decrease of ADMA might be related to the protective role of L-arginine. Changes in the L-arginine pathway are predictive of poststroke infections.

Diabetic neuropathies: diagnosis and management.

INTRODUCTION: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. METHODS: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. CONCLUSION: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective.

Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke.

BACKGROUND: A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined. METHODS: Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay. RESULTS: Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100ß, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent. CONCLUSIONS: Our findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.

Microalbuminuria, indicated by total versus immunoreactive urinary albumins, in acute ischemic stroke patients.

Microalbuminuria, assessed by measuring immunoreactive albumin, is common in patients with cerebrovascular disease and is associated with increased risk of stroke. Total urinary albumin (t-uAlb) comprises both immunoreactive albumin (ir-uAlb) and nonimmunoreactive albumin (nir-uAlb). We hypothesized that t-uAlb is a more sensitive indicator of microalbuminuria than ir-uAlb, and that measurement of t-uAlb will increase the prevalence of microalbuminuria in ischemic stroke patients compared with measurement of ir-uAlb and will show a stronger correlation with the severity of stroke and oxidative stress. In urine samples from 98 patients with ischemic stroke, the albumin-to-creatinine ratios t-uAlb/uCreat and ir-uAlb/uCreat were measured by high-performance liquid chromatography (HPLC) and immunoturbidimetry (IT), and the nir-uAlb/uCreat ratio was calculated. Urinary ortho-tyrosine (o-Tyr/uCreat), an indicator of oxidative stress, was measured by HPLC. The severity of stroke was scored based on the National Institutes of Health Stroke Scale (NIHSS). The prevalence of microalbuminuria detected by HPLC was significantly higher than that detetcted by IT (66.3 vs 36.7%). Although all forms of albumin showed significant correlation with stroke severity (t-uAlb: r = 0.24, P < .05 ir-uAlb: r = 0.25, P < .05 nir-uAlb: r = 0.29, P < .05), only nir-uAlb was found to be an independent predictor of stroke severity (B = 0.20, ß = 0.35, P < .05). In addition, t-uAlb/uCreat and nir-uAlb/uCreat had a significant correlation with o-Tyr/uCreat (r = 0.336, P < .05 and r = 0.358, P < .05 respectively), whereas ir-uAlb/uCreat did not (r = 0.22, P > .05). Our data suggest that in acute ischemic stroke patients, t-uAlb is a more sensitive indicator of microalbuminuria than the presently used ir-uAlb. Future studies should aim to elucidate the underlying mechanisms for the relationship among urinary albumins and cerebrovascular diseases and the role of urinary albumins in risk stratification for stroke.