Peripheral Etiologies Research Articles

Pitfalls and Rewards for Implementing Ocular Motor Testing in Acute Vestibular Syndrome: A Pilot Project.

Isolated acute vestibular syndrome (iAVS) presentations to the emergency department (ED) pose management challenges, given the concerns for posterior circulation strokes. False-negative brain imaging may erroneously reassure clinicians, whereas HINTS-plus examination outperforms imaging to screen for strokes in iAVS. We studied the feasibility of implementing HINTS-plus testing in the ED, aiming to reduce neuroimaging in patients with iAVS. We launched an institutional Quality Improvement initiative, using DMAIC methodology. The outcome measures [proportion of iAVS subjects who had HINTS-plus examinations and underwent neuroimaging by computed tomography/magnetic resonance imaging (CT/MRI)] were compared before and after the established intervention. The intervention consisted of formal training for neurologists and emergency physicians on how to perform, document, and interpret HINTS-plus and implementation of novel iAVS management algorithm. Neuroimaging was not recommended if HINTS-plus suggested peripheral vestibular etiology. If a central process was suspected, brain MRI/MR angiogram was performed. Head CT was reserved only for thrombolytic time-window cases. In the first 2 months postimplementation, HINTS-plus testing performance by neurologists increased from 0% to 80% (P=0.007), and by ED providers from 0% to 9.09% (P=0.367). Head CT scans were reduced from 18.5% to 6.25%. Brain MRI use was reduced from 51.8% to 31.2%. About 60% of the iAVS subjects were discharged from the ED; none were readmitted or had another ED presentation in the ensuing 30 days. Implementation of HINTS-plus evaluation in the ED is valuable and feasible for neurologists, but challenging for emergency physicians. Future studies should determine the "dose-response" curve of educational interventions.

The usefulness of the video head impulse test in children and adults post-concussion.

Dizziness after concussion have been reported in both youths and adults. It is not clear if the dizziness experienced post-concussion is from peripheral or central etiology. New technology has been developed to quickly and easily quantify the magnitude of peripheral vestibular disorders that is non-invasive and acceptable to youths and adults. The purpose of this study was to determine if youths and adults' post-concussion have evidence of decreased horizontal semicircular canal vestibulo-ocular reflex (VOR) gains as measured with the video head impulse test (vHIT), which would indicate a peripheral vestibular disorder. An additional purpose was to determine if VOR gain scores correlate with functional performance measures. Descriptive cross sectional. Large medical center out-patient concussion program. Fifty-six subjects with concussion. Subjects completed the vHIT testing, the Dizziness Handicap Inventory (DHI), the Vestibular Activities and Participation (VAP) scale, the Pediatric Vestibular Symptom Questionnaire, gait speed assessment, the Dynamic Gait Index (DGI) and a verbal analog scale of symptom provocation before and after the vHIT testing. There were no abnormal vHIT findings in any subject. Headaches, dizziness and nausea were significantly worse post vHIT testing (p < 0.05). Youths had better DGI and DHI scores than subjects older than 20 (p < 0.05). The vHIT did not detect horizontal semicircular canal weakness in any of the subjects tested. In addition, older adults reported more activity and participation limitations than the younger subjects with concussion.

Acute vestibular syndrome: a critical review and diagnostic algorithm concerning the clinical differentiation of peripheral versus central aetiologies in the emergency department.

Almost 20% of cerebral ischaemic strokes occur in the posterior circulation. Estimates are that 20% of these patients present with isolated vertigo. In approximately one-sixth to one-third of these patients, this symptom is wrongly diagnosed to be peripheral vestibular in origin. As a result, these missed stroke patients are withheld from therapeutic and secondary prophylactic treatment, which may result in unnecessary morbidity and mortality. We therefore propose a diagnostic algorithm concerning the clinical differentiation of acute vestibular syndrome (AVS) patients based on a critical review of the available literature.

Anticompensatory quick eye movements after head impulses: A peripheral vestibular sign in spontaneous nystagmus.

Differentiating central from peripheral origins of spontaneous nystagmus (SN) is challenging. Looking for a simple sign of peripheral disease with the video Head Impulsive Test we noticed anti-compensatory eye movements (AQEM) in patients with peripheral etiologies of spontaneous nystagmus (SN). Here we assess the diagnostic accuracy of AQEM in differentiating peripheral from central vestibular disorders. We recorded the eye movements in response to horizontal head impulses in a group of 43 consecutive patients with acute vestibular syndrome (12 with central, 31 with peripheral disorders), 5 patients after acute vestibular neurectomy (positive controls) and 39 healthy subjects (negative controls). AQEM were defined as quick eye movements (peak velocity above 50°/s) in the direction of the head movement. All patients with peripheral disorders and positive controls had AQEM (latency 231 ± 53 ms, amplitude 3.4 ± 1.4°, velocity 166 ± 55°/s) when their head was moved to the opposite side of the lesion. Central patients did not have AQEM. AQEM occurrence rate was higher in peripheral patients with contralesional (74 ± 4%, mean ± SD) in comparison to ipsilesional (1 ± 4%) impulses (p< 0.001). Overall diagnostic accuracy for differentiating central from peripheral patients was 96% (95% CI for AUC ROC curve: 0.90 to 1.0) for VOR gain and 100% (95% CI: 1.0 to 1.0) for AQEM occurrence rate. These results suggest that AQEM are a sign of vestibular imbalance in a peripheral deficit. In addition to VOR gain they should be added to the evaluation of the head impulse test.

Restless Leg Syndrome in Neurologic and Medical Disorders.

Adopting prior models of sleep-wake transitions, a flip-flop switch in synchronized neurotransmitter activity is proposed to underlie restless leg syndrome onset. In this model, leg quiescence homeostasis sustained through concerted activities of several neurotransmitters in basal ganglia is perturbed and produces striatal motor activity along sensory activity associated with thalamocortical circuits (conscious urge and discomfort). This model explains the association of restless leg syndrome with a wide variety of associated pathologies emphasizing that perturbed function and imbalance may occur under different steady states of neurotransmitter levels. Likewise, this concept links various central and peripheral etiologies and integrates the augmenting and transient effects of therapeutic neuromodulators.

A multisystem diagnostic mystery: unilateral weakness, a rash, and lymphadenopathy.

A multisystem diagnostic mystery: unilateral weakness, a rash, and lymphadenopathy.

Diagnostic yield and impact of MRI for acute ischaemic stroke in patients presenting with dizziness and vertigo

To identify predictors of acute ischaemic stroke (AIS) and evaluate the diagnostic yield and impact of magnetic resonance imaging (MRI) in patients imaged for dizziness and vertigo. Patients imaged using MRI, including diffusion-weighted imaging (DWI) with or without computed tomography (CT), for dizziness and vertigo over a 2-year period were identified retrospectively. MRI findings were categorised as "acute ischaemic stroke", "significant", or "non-significant". We reviewed the medical records to identify presenting symptoms and signs, vascular risk factors, duration of symptoms, and pre- and post-MRI clinical management in patients with proven stroke. One hundred and eighty-eight patients were included: 39 with vertebrobasilar AIS (20.7%), 32 (17%) with a significant but non-ischaemic abnormality, and 117 (62.2%) with a normal or non-related abnormality. The sensitivity of CT in diagnosing AIS was 9.52% (95% CI: 1.67-31.8%). Posterior inferior cerebellar artery (PICA) territory infarcts were the most common (38.5%). Patients with AIS were significantly more likely to be older than 50 years (p = 0.04), have a greater number of cardiovascular risk factors (p < 0.01), shorter duration of symptoms (p = 0.03), and at least one neurological sign (p = 0.02). DWI MRI had a diagnostic impact on 21.6% patients with stroke. MRI plays an important role in differentiating peripheral and central aetiology when this proves challenging clinically. Predictors of AIS were identified that aid patient selection for MRI, to increase the yield and impact of neuroimaging.

Circulating endothelial progenitor cells and the risk of vascular events after ischemic stroke.

Background and PurposeWe evaluated the hypothesis that the number of circulating EPC could be associated with the risk of stroke recurrence (SR) or vascular events (VE) after an ischemic stroke.MethodsWe studied prospectively consecutive patients with cerebral infarction within the first 48 hours after the onset. We recorded demographic factors, vascular risk factors, previous Rankin scale (RS) score, and etiology. We analyzed EPC counts by flow cytometry in blood collected at day 7 and defined EPC as CD34+/CD133+/KDR+ cells. Mean follow-up was 29.3 ± 16 months. We evaluated SR as well as VE. Patients were classified as to the presence or absence of EPC in the circulation (either EPC+ or EPC-). Bivariate analyses, Kaplan-Meier survival curves and Cox regression models were used.ResultsWe included 121 patients (mean age 70.1±12.6 years; 65% were men). The percentage of EPC+ patients was 47.1%. SR occurred in 12 (9.9%) and VE in 18 (14.9%) patients. SR was associated significantly with a worse prior RS score, previous stroke and etiology, but not with EPC count. VE were associated significantly with EPC-, worse prior RS score, previous stroke, high age, peripheral artery disease and etiology. Cox regression model showed that EPC- (HR 7.07, p=0.003), age (HR 1.08, p=0.004) and a worse prior RS score (HR 5.8, p=0.004) were associated significantly with an increased risk of VE.ConclusionsThe absence of circulating EPC is not associated with the risk of stroke recurrence, but is associated with an increased risk of future vascular events.

Diagnostic value of S100B protein in the differential diagnosis of acute vertigo in the emergency department.

Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining the nature of the vertigo is crucial in the emergency department (ED). With a broad range of potential etiologies, distinguishing central causes from benign peripheral causes is a diagnostic challenge. Cranial magnetic resonance imaging (MRI) is the recommended neuroimaging method when clinical findings are ambiguous. However, MRI scanning for every patient with an uncertain diagnosis may not be efficient or possible. Therefore, to improve ED resource utilization for patients with vertigo, there is a need to identify the subset most likely to have MRI abnormalities. It has previously been shown that S100B protein provides a useful serum marker of stroke, subarachnoid hemorrhage, and traumatic brain injury. This study evaluated whether S100B levels could predict central causes of vertigo as identified by cranial MRI in the ED. This prospective, observational study was conducted with adult patients with acute-onset vertigo (within 6 hours) in the ED of a teaching hospital in Kocaeli, Turkey. Patients with nausea or dizziness complaints without previously known vertigo or cranial pathology, and who agreed to participate in the study, were included. Patients with trauma or with neurologic findings that developed concurrent with their symptoms were excluded. Serum levels of S100B were measured with an electrochemiluminescence immunoassay kit. All subjects underwent cranial MRI. The predictors of positive MRI results were evaluated using logistic regression analysis. Sensitivity and specificity of S100B​ levels for identifying subjects with central causes of vertigo on MRI were calculated with receiver operating characteristic (ROC) curve. Of the 82 subjects included in the study, 48 (58.5%) were female, and the mean (±SD) age was 51 (±16) years. Thirty-one (37.8%) subjects had positive MRI results. Median (with interquartile range [IQR]) serum S100B levels were significantly different between MRI-negative and MRI-positive groups (median = 27.00 pg/mL, IQR = 10.00 to 44.60 vs. median = 60.94 pg/mL, IQR = 38.25 to 77.95, respectively; p = 0.04). In logistic regression analysis, subjective "he or she is spinning" (p = 0.030, odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.38 to 2.49), systolic blood pressure (sBP; p = 0.045, OR = 1.044, 95% CI = 1.021 to 1.080), and serum S100B level (p = 0.042, OR = 1.22, 95% CI = 1.018 to 1.445) were found to be independent predictors of MRI abnormalities. In the ROC analysis, S100B > 30 pg/mL predicted the clinical outcome with 83.9% sensitivity (95% CI = 66.3% to 94.5%) and 51.0% specificity (95% CI = 36.6% to 65.2%). The area under the ROC curve was 0.774 (95% CI = 0.666 to 0.881). To the best of our knowledge this is the first study assessing the utility of serum S100B levels for diagnosis of acute-onset vertigo. Serum S100B levels are associated with the presence of central causes of vertigo on cranial MRI. However, serum S100B levels are not sufficiently sensitive to exclude candidates from cranial MRI.

P323: Anticompensatory quick eye movements after head impulses: a peripheral vestibular sign in spontaneous nystagmus

BACKGROUND: Differentiating central from peripheral origins of spontaneous nystagmus (SN) is challenging. Looking for a simple sign of peripheral disease with the video Head Impulsive Test we noticed anti-compensatory eye movements (AQEM) in patients with peripheral etiologies of spontaneous nystagmus (SN). Here we assess the diagnostic accuracy of AQEM in differentiating peripheral from central vestibular disorders. METHODS: We recorded the eye movements in response to horizontal head impulses in a group of 43 consecutive patients with acute vestibular syndrome (12 with central, 31 with peripheral disorders), 5 patients after acute vestibular neurectomy (positive controls) and 39 healthy subjects (negative controls). AQEM were defined as quick eye movements (peak velocity above 50 ◦ /s) in the direction of the head movement. RESULTS: All patients with peripheral disorders and positive controls had AQEM (latency 231 ± 53 ms, amplitude 3.4 ± 1.4 ◦ , velocity 166 ± 55 ◦ /s) when their head was moved to the opposite side of the lesion. Central patients did not have AQEM. AQEM occurrence rate was higher in peripheral patients with contralesional (74 ± 4%, mean ± SD) in comparison to ipsilesional (1 ± 4%) impulses ( p< 0.001). Overall diagnostic accuracy for differentiating central from peripheral patients was 96% (95% CI for AUC ROC curve: 0.90 to 1.0) for VOR gain and 100% (95% CI: 1.0 to 1.0) for AQEM occurrence rate. CONCLUSIONS: These results suggest that AQEM are a sign of vestibular imbalance in a peripheral deficit. In addition to VOR gain they should be added to the evaluation of the head impulse test.

P324: CNE study of H reflex topography in human calf muscles discloses a dynamic field of motor unit potentials (MUPs) in health and disease

P324: CNE study of H reflex topography in human calf muscles discloses a dynamic field of motor unit potentials (MUPs) in health and disease

The Utility of S100 B Protein in the Differential Diagnosis of Vertigo in the Emergency Department

Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining the nature of the vertigo is crucial in the emergency department (ED). In this broad range of potential etiologies, distinguishing central causes from those benign peripheral causes is a diagnostic challenge for emergency physicians. There is limited knowledge to guide the emergency physician for risk stratification in this wide diagnostic range. Cranial magnetic resonance imaging (MRI) is the suggested neuroimaging method when clinical findings are ambiguous. However, MRI is not readily available in many EDs. Yet, in busy EDs, MRI scanning for each patient with uncertainty in diagnosis may not be efficient in terms of time and cost-effectiveness. Therefore, to improve ED resource utilization in this subset of patients with vertigo, identifying candidates for MRI is important. S100B protein has been shown to be a useful neurobiochemical marker of stroke, subarachnoid hemorrhage, and traumatic brain injury. This study was conducted to evaluate the value of S100B levels for safely discriminating vertigo etiologies to support neuroimaging decisions in EDs.

Periodic alternating nystagmus of peripheral vestibular origin

Periodic alternating nystagmus (PAN) is most commonly found either in its congenital form or after cerebellar/pontomedullary lesions. However, we identified PAN in 10 patients with peripheral vestibular disorders and will try to describe their characteristics to aid in the differential diagnosis between peripheral and central etiologies. Observation of a case series. Peripheral vestibular lesions were confirmed by neurological examinations, vestibular function tests, and brain magnetic resonance imaging (MRIs). Eye movements of the patients were recorded using electronystagmography or video nystagmography for a minimum of 10 minutes to confirm the nystagmus change in direction. The final diagnoses of the patients included Meniere's disease (n = 3), acute labyrinthitis (n = 4), sudden sensorineural hearing loss with vertigo (n = 2), and vestibular schwannoma (n = 1). Direction-changing spontaneous horizontal nystagmus with quiescent intervals was observed in all patients under dark conditions. The nystagmus was suppressed by visual fixation; and the results of oculomotor tests were normal for saccadic and smooth pursuit eye movements and optokinetic nystagmus. All patients showed mild to complete canal paresis on a bithermal caloric test. PAN progressed into unidirectional nystagmus of the contra-lesion side in all patients within 48 hours. PAN can be observed in patients with peripheral vestibular disorders, but detecting PAN in this subpopulation is difficult because of its transitory nature. The absence of central symptoms and signs, the visual suppression of PAN, normal oculomotor tests, and transient persistence are important diagnostic clues for differentiating peripheral from central PAN. 4.

Endocrine management of children with Prader&amp;ndash;Willi syndrome

Endocrine management of children with Prader&ndash;Willi syndrome Clarice Borschiver Medeiros,1 Ana Paula Bordallo,1 Flavio Moutinho Souza,2 Paulo Ferrez Collett-Solberg1,31Endocrinology Unit, Departamento de Medicina Interna, Faculdade de Ci&ecirc;ncias M&eacute;dicas, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil; 2Pediatric Endocrinology Unit, Departamento de Pediatria, Hospital Federal Cardoso Fontes &ndash; Minist&eacute;rio da Sa&uacute;de do Brasil, Bras&iacute;lia, Brazil; 3Laborat&oacute;rio de Pesquisas Cl&iacute;nicas e Experimentais em Biologia Vascular (BioVasc), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, BrazilAbstract: Prader&ndash;Willi syndrome is a rare genetic condition afflicting nearly 1/15,000 live births. Clinical features include neonatal hypotonia, poor weight gain in early infancy followed by binge eating from childhood to adulthood, severe obesity, developmental delay, short stature, and hypogonadism of both central and peripheral etiology. Central hypothyroidism and adrenal insufficiency may occur. Sleep disordered breathing, by obstruction of upper airways associated with central hypoventilation, is a common feature. Most of these characteristics are assumed to be the result of a hypothalamic dysfunction. The most important complication and the most difficult to manage is the obesity. This review aims at discussing the most recent strategies to manage the endocrine complications of Prader&ndash;Willi syndrome patients, with a special approach on the treatment of obesity, hypogonadism, and short stature. We summarize the indication and effects of recombinant human growth hormone therapy on growth, cognitive development, and body composition, and discuss the effects of recombinant human growth hormone therapy on the resulting sleep disorders.Keywords: Prader&ndash;Willi syndrome, obesity, hypogonadism, growth hormone, sleep disorder

Using Pulsed Radiofrequency Ablation to Treat Pain Associated with a Tumor Involving the Brachial Plexus

Pain associated with cancer is often difficult to treat, even more so when tumors involve peripheral nerves. Therapy is complex and often requires a multimodal approach that can include medications, radiation, and interventional techniques. These components are utilized with variable success, but are also limited by known complications or adverse effects. We present the case of a 53-year-old woman with a metastatic axillary tumor that involved her brachial plexus. Attempts to control her pain with medication were unsuccessful despite escalation and use of adjunct agents. She was not deemed to be a surgical candidate due to the size and location of the tumor. Radiation was discussed but, obviously, would not work immediately. Our team decided to employ a brachial plexus catheter for continuous nerve block, which provided almost complete relief of pain. Since her pain was deemed to be of peripheral etiology, pulsed radiofrequency ablation of her brachial plexus was used for more long-term pain relief. The patient responded very well with minimal pain issues and no apparent complications. On follow-up, the patient had good relief for almost 2 months. Pulsed radiofrequency is a poorly understood technology that has increasing evidence for certain pain conditions; however, for cancer and peripheral nerves the evidence is slim to none. Our case presents a successful use for pain management of a brachial plexopathy due to a tumor. We propose that pulsed radiofrequency may present a non-neurodestructive pain management technique for tumors involving peripheral nerves, though more data is definitely needed. Key words: Pulsed radiofrequency, brachial plexopathy, brachial plexus, tumor, cancer, pain

Neuromuscular hamartoma of the sciatic nerve: Case report and review of the literature

Background:Neuromuscular hamartomas are rare benign tumors with mature skeletal elements mixed with mature neural elements. They present typically as solitary lesions in childhood and have been reported to be associated with cranial nerves or large peripheral nerves such as the brachial plexus, median nerve, and sciatic nerve. To date, eight cases of sciatic nerve neuromuscular hamartomas have been reported. We present a case along with an outline for the natural history of the disease with a review of the literature of the reported cases dating back to 1895.Case Description:An 11-year-old boy presented with progressive right lower extremity pain and atrophy. Magnetic resonance imaging revealed a large right sciatic nerve mass, and electromyography demonstrated evidence of ongoing denervation and reinnervation. Initial computed tomography-guided biopsy was unrevealing and subsequent open biopsy was consistent with neuromuscular choristoma.Conclusion:Neuromuscular choristomas represent a rare disease. Symptoms of foot deformity, leg size discrepancy, and pain merit a complete work-up including spinal and peripheral nerve etiologies.

Treatment of Phantom Limb Pain by Cryoneurolysis of the Amputated Nerve

The pathophysiology of phantom limb pain (PLP) is multifactorial. It probably starts in the periphery and is amplified and modified in the central nervous system. A small group of patients with PLP were questioned as to the portion of the phantom limb affected by pain (e.g., "great toe," "thumb"). In the stump, the corresponding amputated nerve was located with a nerve stimulator. With correct placement and stimulation, the PLP could then be reproduced or exacerbated. A small dose of local anesthesia was then injected, resulting in the disappearance of the PLP. If a peripheral nerve injection gave temporary relief, our final treatment was cryoanalgesia at this location. Evaluation of 5 patients, followed for at least 2.5 years, yielded the following results: 3 patients had excellent results (100%, 95%, and 90% decrease in complaints, respectively), 1 patient had an acceptable result (40% decrease), and 1 patient had only a 20% decrease in pain. Although both central and peripheral components are likely involved in PLP, treatment of a peripheral pain locus with cryoanalgesia should be considered. We propose the identification of a peripheral etiology may help match patients to an appropriate therapy, and cryoanalgesia may result in long-term relief of PLP.

The incidence and etiology of community-acquired pneumonia in fever outpatients

The purpose of this study was to analyze the incidence, etiology and clinical characteristics of community-acquired pneumonia (CAP) among outpatients with sore throat and/or cough, and thus to provide theoretical basis for timely and accurate diagnosis and treatment for CAP. We used chest X-rays for fever (a temperature greater than 37.5°C) patients, who were recruited since 2007, presenting with sore throat and/or cough. The patients' age, gender, days of fever, respiratory symptoms (e.g. cough and sputum), peripheral blood count and etiology (pathogens) of CAP were recorded. Of all the 6539 fever outpatients, those aged 10-39 and above 60 years old accounted for 61.0% and 15.6%, respectively. In total, 402 were diagnosed with CAP with an incidence rate of 6.1%. Among them, 38.1% were above 60 years old. The prevalence increased with age. Of the 402 CAP patients, 36.8% (148/402) presented no respiratory symptoms and 30.1% (121/402) had positive etiology. The top three pathogens were Mycoplasma pneumoniae (23.1%), Streptococcus pneumoniae (17.3%) and Haemophilus influenzae (9.1%). Among the 121 etiology-positive patients, 14 cases were mixed infections (at least one atypical pathogen). Nine cases were M. pneumoniae mixed with bacterial/virus infection, and five cases were Chlamydia pneumoniae mixed with other bacteria/mycoplasma infection. We found that fever outpatients have a higher prevalence of CAP, which increases with age, i.e. older people are more susceptible to CAP. S. pneumoniae and H. influenzae are common pathogens in CAP; however, atypical pathogens, especially M. pneumoniae, remain the most common pathogens in CAP.

Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation

BackgroundPatients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU) is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study.MethodsThe INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation) registry is the first to provide large scale data on 1,167 patients with acute stroke (< 3 months) that survived the initial phase of high risk and were undergoing neurologic in-patient rehabilitation. MAU was determined by dipstick-testing and correlated to baseline clinical variables (stroke-origin, functional impairment, co-morbidity, ankle-brachial-index, intima-media-thickeness) as well as vascular events after one year of follow-up. Comparisons were made with the χ2 or Mann–Whitney-U Test. Relative risks (RR) with 95% confidence intervals (CI) were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR) using Cox proportional hazard regression.ResultsA substantial proportion of patients was MAU positive at baseline (33.1%). Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p < 0.0001), had a slightly higher body mass index (27.8 vs. 27.1 kg/m2; p = 0.03) and increased waist circumference (79.5 vs. 50.4% for women [p < 0.0001] and 46.8 vs. 43.2% for men [p = 0.04]) and twice as often had diabetes mellitus (41.8 vs. 20.1%; p < 0.0001). Patients with MAU had a similar NIH stroke scale score (median 3 vs. 3; p = 0.379) but had lower values on the Barthel Index (median 75 vs. 90; p < 0.001). They had higher rates of atrial fibrillation (RR 1.38; 95% CI 1.09-1.75), coronary artery disease (RR 1.54; 95% CI 1.18-2.00), heart failure (RR 1.70; 95% CI 1.10-2.60) symptomatic peripheral artery disease (RR 2.30; 95% CI 1.40-3.80) and atherosclerotic stroke etiology (53.7 vs. 35.4%; p < 0.0001). MAU was associated with an increased intima-media-thickness, decreased ankle-brachial-index and polyvascular disease (RR 1.56; 95%CI 1.31-1.99). The event rate after a median follow-up of 13 months was 6.7% for fatal or nonfatal stroke, 4.7% for death, and 10.9% for combined vascular events (stroke, MI, vascular death). The presence of MAU was predictive for vascular events during the following year (HR for total mortality 2.2; 95% CI 1.3-3.7; HR for cardiovascular events 2.3; 95% 1.2 - 4.4).ConclusionsINSIGHT demonstrated a significant association between MAU and polyvascular disease and further supports previous findings that MAU predicts cardio-/cerebrovascular events in patients recovering from ischemic stroke. This biomarker may also be used in patients during neurologic in-patient rehabilitation, opening a window of opportunity for early intervention in this patient group at increased risk for recurrent events.

Congenital hypothyroidism

Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency present at birth. Babies with CH who are not identified and treated promptly develop severe mental retardation. Most of the babies with CH do not manifest the typical known signs and symptoms of hypothyroidism, and this is most likely due to transplacental passage of some maternal thyroid hormone in addition to some residual neonatal thyroid function, as might be seen with thyroid hypoplasia, an ectopic gland, or mild dyshormonogenesis. Screening for CH has enabled the virtual eradication of the devastating effects of mental retardation due to sporadic CH in most developed countries of the world. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Permanent CH refers to a persistent deficiency of thyroid hormone that requires life-long treatment. Transient CH refers to a temporary deficiency of thyroid hormone that is discovered at birth but recovers to normal in the first few months or years of life. In the last several decades, there have been exciting advances in our understanding of fetal and neonatal thyroid physiology. In addition, advances in molecular biology have helped in understanding the early events in thyroid gland embryogenesis, mechanisms of thyroid action in the brain, the molecular basis for many of the inborn errors of thyroid hormonogenesis, and thyroid hormone action. However, many questions and challenges are still not answered. For example, the increasing numbers of surviving small and premature neonates with abnormalities in thyroid function need definite diagnostic criteria and whether they require medical therapy. Another challenge is the dilemma of finding the best screening methodology that is sensitive and cost effective.