Muscle mass as a modifier of stress response in acute ischemic stroke patients.

Stroke triggers a systemic inflammatory response over the ensuing days after the cerebral insult. The age and comorbidities of the stroke population make them a vulnerable population for low muscle mass and sarcopenia, the latter being another clinical condition that is closely associated with inflammation, as shown by increased levels of pro-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR). In this study, we evaluated the relationship between post-stroke NLR changes and muscle mass in a prospective cohort of acute ischemic stroke patients (n = 102) enrolled in the Muscle Assessment in Stroke Study Turkey (MASS-TR). Admission lumbar computed tomography images were used to determine the cross-sectional muscle area of skeletal muscles at L3 vertebra level and calculate the skeletal muscle index (SMI). The median (IQR) SMI was 44.7 (39.1-52.5) cm2/m2, and the NLR at admission and follow-up were 4.2 (3.0-10.5) and 9.4 (5.7-16.2), respectively. While there was no relationship between SMI and admission NLR, a significant inverse correlation was observed between SMI and follow-up NLR (r = - 0.26; P = 0.007). Lower SMI remained significantly associated (P = 0.036) with higher follow-up NLR levels in multivariate analysis. Our findings highlight the importance of muscle mass as a novel factor related to the level of post-stroke stress response.

Determinants of in-hospital muscle loss in acute ischemic stroke - Results of the Muscle Assessment in Stroke Study (MASS).

BACKGROUND & AIMS: There is a change in the mass and composition of paretic and non-paretic skeletal muscles in the chronic phase of stroke. The multi-center, prospective, and observational Muscle Assessment in Stroke Study (MASS) was performed to evaluate the degree of muscle loss during the in-hospital acute stroke setting and determine factors contributing to this loss. METHODS: Acute dysphagic ischemic stroke patients (n = 107) admitted to neuro-intensive care units were evaluated by computed tomography on days 1 and 14 after admission to determine the cross-sectional muscle area (CSMA) at the level of the mid-humerus, mid-thigh, and third lumbar vertebra. The percentage change in CSMA and variables associated with this change were evaluated by univariate and multivariate analyses. RESULTS: There were significant reductions in CSMA in all the muscle groups analyzed; the most prominent change was observed in the arms (both: 14.2 ± 10.7%; paretic: 17.7 ± 11.6%; non-paretic: 10.1 ± 12.5%), followed by the muscles in the legs (both: 12.4 ± 8.7%; paretic: 12.9 ± 9.9%; non-paretic: 12.0 ± 9.3%) and L3-vertebra level (5.6 ± 9.8%) (P < 0.001 for all). Higher calorie (r = -0.378, P < 0.001) or protein (r = -0.352, P < 0.001) intake was negatively associated with the decrease in CSMA of upper extremities. A substantial protein (≥0.4 g/kg/d) or calorie (≥5 kcal/kg/d) gap between targeted or actual intake was related to a larger decrease in CSMA in all the anatomic regions (P ≤ 0.05 for all). Other significant predictors of muscle loss included history of diabetes mellitus, male sex, higher BMI, in-hospital infections, and the necessity for invasive mechanical ventilation. CONCLUSIONS: There is a considerable degree of loss in the global muscle mass in acute ischemic stroke patients over a two-week period. Along with several factors, falling significantly behind the daily protein or calorie targets was related to the decrease in the muscle area. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov identifier NCT03825419.

Optimal use of oral nutritional supplements (ONS) in medical nutrition therapy: ONS consensus report from KEPAN.

Medical nutrition therapy is one of the core components of the patient management, although its implication is still limited in daily practice globally. Clinicians are in need of guidance that will ease the application of medical nutrition therapy. The first treatment choice in medical nutrition therapy is the use of oral nutritional supplements (ONS) after or concomitant with dietary interventions. The pre and post-graduate curriculum for medical nutrition therapy is limited in most regions, worldwide. A report that is short, clear, and having clear-cut recommendations that will guide the primary healthcare professionals in indications, choice, practical application, follow-up, and stopping ONS would facilitate the application and success of medical nutrition therapy. KEPAN is the Clinical Enteral and Parenteral Nutrition Society of Turkey and is an active member of the European Society for Clinical Nutrition and Metabolism (ESPEN). In this study, we present the KEPAN ONS consensus report on optimal ONS use in medical nutrition therapy as outlined by works of academicians experienced in clinical application of ONS (eight working group academicians and 19 expert group academicians). This report provides 22 clear-cut recommendations in a question-answer format. We believe that this report could have a significant impact in the ideal use of ONS in the context of medical nutrition therapy when clinicians manage everyday patients.

Which Ischemic Stroke Subtype Is Associated with Hyperhomocysteinemia?

BACKGROUND: Stroke is still a major global health problem in both developed and developing countries. Defining stroke subtype and underlying etiologies is a major step to choose the best method for prophylaxis. Homocysteine is an endothelial toxin and elevated levels have been associated with stroke risk. In this study, we hypothesized that serum total homocysteine level may be related with specific atherothrombotic ischemic stroke subtypes and aimed to find if high serum homocysteine levels are correlated with any specific ischemic stroke subtype. METHODS: Patients with ischemic stroke and aged between 18 and 65 are included. Ischemic stroke subtype is defined according to Causative Classification System. Hospital records are examined retrospectively to define patient demographics, ischemic stroke subtype, vascular risk factors, serum homocysteine, B12, and folic acid levels. RESULTS: A total of 262 patients were included. Serum homocysteine level was elevated (≥16 µmol/L) in 99 patients (37.79%). The rate of patients with hyperhomocysteinemia was significantly more common in strokes due to intracranial stenosis (72.41%) (odds ratio 8.138; 95% confidence interval 2.366-27.989; P < .01) than extracranial large artery stenosis (52.00%), craniocervical arterial dissections (35.71%), cardioembolic strokes (27.87%), and lacunar infarctions (25.00%) after adjustment for other risk factors. High homocysteine levels were significantly more common in men and smokers (P < .05). CONCLUSIONS: Elevated levels of serum homocysteine are correlated with ischemic strokes due to intracranial large artery stenosis in young and middle-aged patients. This association may have an implication in stroke prophylaxis for intracranial atherosclerosis by using homocysteine-lowering therapies.

The correlation of the platelet-to-lymphocyte ratio with the severity of stenosis and stroke in patients with carotid arterial disease.

Objectives Platelet-to-lymphocyte ratio is a novel biomarker, recently shown to be correlated with atherosclerotic inflammation. This study investigated the role of platelet-to-lymphocyte ratio in patients with carotid artery stenosis and stroke. Methods Patients, who underwent carotid angiography with Multiple Detector Computed Tomography Angiography at our hospital, were retrospectively screened. Patients enrolled were divided into three groups based on the platelet-to-lymphocyte ratio. Patients with a platelet-to-lymphocyte ratio value between 55.0 and 106.71 were assigned to Group I, patients with a platelet-to-lymphocyte ratio value between 106.79 and 160.61 were assigned to Group II and patients with a platelet-to-lymphocyte ratio value between 162.96 and 619.61 were assigned to Group III. The carotid arterial stenosis calculated was classified as per the criteria of North American Symptomatic Carotid Endarterectomy Trial. Results One hundred fifty patients were included in our trial (mean age 61.9 ± 13.1 with 104 males). The rate of carotid arterial stenosis was detected to be higher in patients with a high platelet-to-lymphocyte ratio value (p = 0.010). Additionally, the platelet-to-lymphocyte ratio was positively correlated with the carotid arterial stenosis percentage (r = 0.250, p = 0.002). In the multi-variate regression analysis, platelet-to-lymphocyte ratio was detected to be an independent variable with respect to stroke (odd's ratio = 1.012, confidence interval = 1.001-1.024, p = 0.031). Conclusions Increased platelet-to-lymphocyte ratio could be a simple and practical marker of the clinical course in patients with carotid arterial stenosis.

Prediction of Early Recurrence After Acute Ischemic Stroke.

IMPORTANCE: Approximately half of recurrent strokes occur within days and weeks of an ischemic stroke. It is imperative to identify patients at imminent risk of recurrent stroke because recurrent events lead to prolonged hospitalization, worsened functional outcome, and increased mortality. OBJECTIVE: To test the validity of a prognostic score that was exclusively developed to predict early risk of stroke recurrence in a multicenter setting. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based cohort study examined patients with and without magnetic resonance imaging-confirmed recurrent stroke within 90 days after an ischemic stroke. The study was performed at 3 teaching hospitals in the United States, Brazil, and South Korea and comprised adult patients admitted within 72 hours of symptom onset with a magnetic resonance imaging-confirmed diagnosis of acute ischemic stroke. Recruitment to the US cohort was performed from June 1, 2009, through April 30, 2011. Recruitment to the Korean and Brazilian cohorts was performed from January 1, 2007, through December 31, 2011. Data analysis was performed from June 1, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent ischemic stroke as defined by a clinical incident that was clearly attributable to a new area of brain infarction occurring within the 90 days of index infarction. An investigator who was masked to the patient's recurrence status calculated the Recurrence Risk Estimator (RRE) score for each patient based on information available after initial line of testing in the emergency department. We assessed the predictive performance of the RRE by computing the area under the receiver operating characteristic curve. RESULTS: The study included 1468 consecutive patients with 59 recurrent ischemic stroke events. The median age of the patients was 69 (interquartile range, 58-79) years, and 633 (43.1%) were female. The cumulative 90-day recurrence rate was 4.2% (95% CI, 3.2%-5.2%). The mean RRE score was 2.2 (95% CI, 1.9-2.5) in patients with recurrence and 1.0 (95% CI, 1.0-1.1) in patients without. The risk of recurrence increased with a higher RRE score (log-rank test, P < .001). The area under the receiver operating characteristic curve for discrimination was 0.76 (95% CI, 0.70-0.82). The RRE identified 710 patients (48.4%) in the study population as high risk (>10%) or low risk (<1%). The sensitivity and specificity were 38% and 93% for identifying low-risk subsets and 41% and 90% for identifying high-risk subsets, respectively. CONCLUSIONS AND RELEVANCE: This study confirms the validity of the RRE score in a multicenter cohort of patients with diverse characteristics. Our findings suggest that the RRE could be useful in identifying high- and low-risk patients for targeted stroke prevention.

Analyses of the Turkish National Intravenous Thrombolysis Registry.

BACKGROUND: The relatively late approval of use of recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke in Turkey has resulted in obvious underuse of this treatment. Here we present the analyses of the nationwide registry, which was created to prompt wider use of intravenous thrombolysis, as well as to monitor safe implementation of the treatment in our country. METHODS: Patients were registered prospectively in our database between 2006 and 2013. Admission and 24-hour National Institutes of Health Stroke Scale and 3-month modified Rankin Scale scores were recorded. A "high-volume center" was defined as a center treating 10 or more patients with rt-PA per year. RESULTS: A total of 1133 patients were enrolled into the registry by 38 centers in 18 cities. A nearly 4-fold increase in the study population and in the number of participating centers was observed over the 6 years of the study. The mean baseline NIHSS score was 14.5 ± 5.7, and the prevalence of symptomatic hemorrhage was 4.9%. Mortality at 3 months decreased from 22% to 11% in the 6 years of enrollment, and 65% of cases were functionally independent. Age older than 70 years, an NIHSS score higher than 14 upon hospital admission, and intracranial hemorrhage were independently associated with mortality, and being treated in a high-volume center was related to good outcome. CONCLUSIONS: We observed a decreasing trend in mortality and an acceptable prevalence of symptomatic hemorrhage over 6 years with continuous addition of new centers to the registry. The first results of this prospective study are encouraging and will stimulate our efforts at increasing the use of intravenous thrombolysis in Turkey.

Pathophysiologic, rather than laboratory-defined resistance drives aspirin failure in ischemic stroke.

BACKGROUND: A significant proportion of ischemic strokes occur while using aspirin and therefore can be considered as clinical aspirin resistance. Apart from this clinical description, aspirin resistance can be defined by laboratory tests of in vitro platelet reactivity. The correlation between clinical and laboratory-defined resistance, however, is far from perfect, and the heterogenous nature of stroke pathophysiology might play a role in this discrepancy. METHODS: The level of in vitro platelet inhibition by aspirin was prospectively evaluated using the VerifyNow Aspirin Assay (Accumetrics, San Diego, CA) in patients presenting with ischemic stroke while using aspirin (n = 78). Demographic and clinical features, including stroke etiology, were compared among patients with and without sufficient level of platelet inhibition and an additional set of patients suffering from stroke while not using aspirin (n = 257). Similar analyses were performed in a separate validation cohort. RESULTS: Laboratory evidence of insufficient platelet inhibition was detected in 16 of 78 patients (21%) with clinical aspirin resistance. On the other hand, 30 patients (38%) had stroke etiologies well known to be inadequately responsive to aspirin therapy. Overall, laboratory-defined resistance by itself could be considered to be accountable for the ischemic event in only 15% of these patients. The corresponding figure was 9% in validation cohort. Patients with sufficient level of platelet inhibition were more likely to harbor an anticoagulant responsive etiology compared with aspirin naive patients (odds ratio, 2.0; P = .033). CONCLUSIONS: Our findings highlight that laboratory aspirin resistance because of insufficient platelet inhibition is relatively uncommon, whereas pathophysiologic resistance, signifying the presence of etiologies that cannot be efficiently treated with aspirin treatment, is a major contributor of clinical resistance in ischemic stroke.

Optic neuropathy secondary to inflammation of sphenoidal sinuses and Onodi cell polyps: a case report.

An inflammation or injury to optic nerve anywhere its pathway by extrinsic lesions causes the optic neuropathy. These lesions are more effective in confined spaces like optic canal, orbital apex. We present a 61 year old woman with optic neuropathy due to lesion in an Onodi cell. In this case patient presented with progressive loss of vision in her right eye within a few days. Computed tomography (CT) revealed mucosal thickening and inflammatory signs in right sphenoid sinus and presence of Onodi cell in that side. Magnetic Resonance Imaging confirmed compression to the optic nevre. Systemic antibioterapy and endoscopic sinus surgery was performed. Postoperatively, the visual acuity and control CT views were better than initial findings. Histopathologic evaluation revealed polyps in Onodi cell. Ophthalmologists should be aware of the Onodi cell pathologies that caused compressive optic neuropathy.

Is symptomatic atherosclerotic cerebrovascular disease a risk factor for normal-tension glaucoma?

OBJECTIVE: To compare the incidence of glaucomatous optic disk appearance between patients with symptomatic atherosclerotic stroke and healthy individuals with normal intraocular pressures (IOP). SUBJECTS AND METHODS: 46 patients with ischemic stroke with evident lacunar infarction or large vessel atherosclerosis, and 93 age- and sex-matched healthy individuals, all with normal IOP, were included. Patients and controls were examined for the presence of high cup-to-disk ratios (> 0.5). RESULTS: Seven patients (15.22%) in the ischemic cerebrovascular disease (CVD) group and 3 controls (3.23%) had glaucomatous optic disk appearance. All subjects with glaucomatous optic disk appearance in the control group and 3 patients in the study group had visual field defects in concordance with normal-tension glaucoma (NTG). The incidence of glaucomatous optic disk appearance was significantly higher in the group with symptomatic atherosclerotic CVD. CONCLUSION: Atherosclerotic CVD is a risk factor for having glaucomatous optic disk appearance. Symptomatic atherosclerosis involving the brain vasculature may also affect the eye and lead to NTG. Patients with ischemic strokes due to large artery atherosclerosis or small artery occlusion must be examined and followed for NTG.

Visual evoked potentials in guillain-barré syndrome.

BACKGROUND AND PURPOSE: Guillain-Barré syndrome (GBS) is an acute demyelinating polyneuropathy with various clinical features. Optic neuritis occurs in rare cases. In this study we determined the incidence and patterns of visual evoked potential (VEP) abnormality in GBS in association with ophthalmologic findings. METHODS: Thirty-two patients with a diagnosis of GBS were included in the study. The correlation between pathologic VEPs and categories of neurologic deficit and electrophysiological findings were examined statistically. RESULTS: The patients ranged in age from 19 to 77 years. Five cases (16%) had abnormal VEPs. All five of these patients exhibited increased P100 latency differences between the two eyes. Other abnormalities were prolonged p100 latency, increased interocular amplitude difference, and distorted p100 configuration. Pathologic signs on ophthalmologic examination were observed in 80% of patients with abnormal VEPs. VEP abnormality was never present in pure axonal forms. There was no significant correlation between pathologic VEP and cerebrospinal fluid protein level or categories of neurologic deficits. CONCLUSIONS: Involvement of the optic pathways is not a frequent finding in GBS. When present it is always asymmetric and generally accompanied with pathologic findings on ophthalmologic examination. VEPs may be abnormal in different clinical variants of GBS, and especially in demyelinating forms.

Does long term use of piracetam improve speech disturbances due to ischemic cerebrovascular diseases?

Aphasia causes significant disability and handicap among stroke survivors. Language therapy is recommended for aphasic patients, but not always available. Piracetam, an old drug with novel properties, has been shown to have mild beneficial effects on post-stroke aphasia. In the current study, we investigated the effects of 6 months treatment with piracetam on aphasia following stroke. Thirty patients with first-ever ischemic strokes and related aphasia were enrolled in the study. The scores for the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), and Gülhane Aphasia Test were recorded. The patients were scheduled randomly to receive either 4.8 g piracetam daily or placebo treatment for 6 months. At the end of 24 weeks, clinical assessments and aphasia tests were repeated. The level of improvement in the clinical parameters and aphasia scores was compared between the two groups. All patients had large lesions and severe aphasia. No significant difference was observed between the piracetam and placebo groups regarding the improvements in the NIHSS, BI and mRS scores at the end of the treatment. The improvements observed in spontaneous speech, reading fluency, auditory comprehension, reading comprehension, repetition, and naming were not significantly different in the piracetam and placebo groups, the difference reached significance only for auditory comprehension in favor of piracetam at the end of the treatment. Piracetam is well-tolerated in patients with post-stroke aphasia. Piracetam taken orally in a daily dose of 4.8 g for 6 months has no clear beneficial effect on post-stroke language disorders.

Admission international normalized ratio and acute infarct volume in ischemic stroke.

OBJECTIVE: The level of anticoagulation at the time of stroke onset may influence the size, composition, and dissolution rate of the occlusive clot. We explored the relation between admission international normalized ratio (INR) and acute infarct volume in patients with ischemic stroke. METHODS: We studied 93 consecutive patients with preadmission warfarin use who had INR measurement and diffusion-weighted imaging performed within 24 hours of stroke onset. Ninety-three etiologic stroke subtype-matched patients without prior warfarin use served as control patients. Linear regression analysis was used to test for independence of INR as a predictor of infarct volume. RESULTS: In patients with preadmission warfarin use, admission INR was inversely correlated with lesion volume on diffusion-weighted imaging (r = -0.38). This relation was retained after adjustment for potential covariates (p = 0.014). INR less than 2.0 was associated with 3.5-fold (95% confidence interval, 2.9-4.2) greater lesion volume on diffusion-weighted imaging as compared with INR of 2.0 or more. Patients who were on therapeutic INR (>or=2.0) had smaller infarcts compared with patients without preadmission warfarin use (p = 0.001). Admission INR was inversely correlated with acute perfusion defect (r = -0.33), chronic infarct volume (r = -0.42), National Institutes of Health Stroke Scale score at admission (r = -0.27), and modified Rankin score at discharge (r = -0.28). INTERPRETATION: These results suggest that preadmission warfarin use associated with therapeutic level of anticoagulation can offer a benefit in limiting the extent of ischemic injury in an event of acute stroke.

Hypothyroid myopathy with manifestations of Hoffman's syndrome and myasthenia gravis.

Although hypothyroid myopathy is seen frequently and the relationship with autoimmune hypothyroidism and myasthenia gravis is well known, specific forms of hypothyroid myopathy such as Hoffman's syndrome (HS) are rarely described. Here we describe a 40-year-old patient with Hashimoto thyroiditis showing symptoms and signs of two discrete forms of hypothyroid myopathy (HS and myasthenic syndrome) together. To our knowledge this is the first reported case with features of both of these syndromes. We discuss the diagnosis, speculate whether this patient may represent a unique form of hypothyroid myopathy, and report the 6-month follow-up of the patient both clinically and electrophysiologically.

Rapid identification of disease-causing mutations using copy number analysis within linkage intervals.

SNP and comparative genome hybridization arrays (aCGH) are powerful techniques for identifying genome rearrangements, deletions, and duplications. We hypothesized that current array-based detection of copy number variation (CNV) could complement parametric linkage analysis and allow the rapid identification of functional mutations in families with inherited disorders. Herein, we demonstrate the utility of this technique by rapidly identifying a disease causing microdeletion within the PARK2 gene in a family with autosomal recessive Parkinsonism.

Effect of heating on nerve conduction in carpal tunnel syndrome.

The effect of temperature on normal nerves is well known, i.e., an increase in conduction velocity and a decrease in amplitude with an elevation in temperature. There are few reports examining the effect of temperature on abnormal nerves, e.g., in demyelination. To study the effect of increased temperature on demyelinating nerves in entrapment syndromes, the authors investigated 55 median and 48 ulnar nerves of 48 patients with carpal tunnel syndrome, and 48 median and 48 ulnar nerves of 26 healthy subjects. All measurements were obtained at 32 degrees C and 37 degrees C. Mean reductions in median sensory amplitude occurring with heating were significantly greater in the patient group than in the control group (P = 0.000). For median sensory response amplitude, the mean decrease was 32.1% in patients with carpal tunnel syndrome and 10.7% in the control subjects. The difference between median and ulnar nerves in the latency was significantly decreased (P = 0.027) after the nerves had heated to 37 degrees C. It is concluded that the elevation in temperature leads to conduction block in demyelinated sensory nerves, and that temperature provocation may be useful in the diagnosis of nerve disorders. The effect may be different in axonal and demyelinating disorders.

Dyke-Davidoff-Masson syndrome.

We reported five cases of Dyke-Davidoff-Masson syndrome (DDMS) with different clinical and radiological findings. The evaluated parameters were the location of the lesions, midline structural shift effect, pathological and morphological changes on the ipsilateral calvarium, paranasal sinuses and mesencephalon, presence of compensatory contralateral hypertrophy. With the help of both magnetic resonance (MR) and computerized tomography (CT) images, changing degrees of all the evaluated parameters were observed in all five of our patients. In conclusion, no relationship was found between parenchymal and calvarial changes and between the time after onset of the disease and amount of the morphologic and pathological changes.