Foot skin blood flow following infrainguinal revascularization for critical lower limb ischemia.

INTRODUCTION: The aim of this study was to assess the blood flow in the feet before and after lower limb revascularization using laser Doppler imaging (LDI). METHODS: Ten patients with critical lower limb ischemia were prospectively enrolled from June to October 2004. All patients underwent successful unilateral surgical interventions including above-knee bypass, distal bypass and endarterectomy. Skin blood flow (SBF) over the plantar surface of both forefeet and heels was measured by LDI 24h before and 10 days after revascularization, expressed in perfusion units (PU), and reported as mean+/-SD. RESULTS: Measurements in the forefoot and heel were similar. Before revascularization mean SBF was significantly lower in the ischemic foot (130+/-71 PU) compared to the contralateral foot (212+/-68 PU), p<0.05. After revascularization a significant increase of the SBF in the forefoot (from 135+/-67 to 202+/-86 PU, p=0.001) and hindfoot (from 148+/-58 to 203+/-83, p=0.001) was observed on the treatment side. However, a large decrease of the SBF was seen in forefoot and hindfoot on the untreated side (from 250+/-123 PU to 176+/-83 and from 208+/-116 to 133+/-40, p=0.001, respectively). CONCLUSION: This study confirms the benefits of revascularization in patients with nonhealing foot lesions due to critical limb ischemia. A significant increase of the SBF was observed on the treatment side. However, an unexpected decrease was observed on the untreated side.

Acquisitions thérapeutiques en médecine ambulatoire en 2011 [2011 findings from literature on general internal ambulatory medicine].

In 2011 several articles seemed significant for the practice of general medicine. Diagnosis of hypertension needs several measurements and may need 24-hour ambulatory blood pressure monitoring. Glycosylated hemoglobin is a reliable tool to diagnose diabetes mellitus. The ABCD2 score with neurological imaging help the triage of transient ischemic attacks. Pulmonary embolism can be treated as outpatient for low risk patients. Gluten-free diet may be tried in irritable bowel syndrome. Nitrofurantoin is a reasonable alternative for simple urinary tract infection in women, but antibiotics are not needed after drainage of an uncomplicated skin abscess. Subclinical thyroid dysfunction is a risk factor of osteoporosis in older men. Sequential use of MMSE and ACE scores is a promising approach to assess medical decision-making capacity.

First aid in burn injuries with counterintuitive warm water improves outcome

Objective: Cooling is considered a panacea in burn injury. However, burn injuries are characterized by an ischemic zone prone to progression, a phenomenon that can substantially increase morbidity. Cold-induced vasoconstriction potentially aggravates ischemia and promotes progression. Therefore we compared the effect of warm (37°C) and cold (17°C) water on burn progression. Methods: The comb burn model creates 4 rectangular burned surfaces separated by 3 unburned interspaces that become necrotic if untreated. After heating in boiling water the template was applied for 60 seconds on 24 Wistar rats randomized into 3 groups: no treatment (CON); treatment for 20 minutes with cold water (17°C: CW) or warm water (37°C: WW). Burn progression in surface (planimetry) and Departmenth (histology), as well as microcirculatory perfusion (laser Doppler flowmetry) were assessed after 1h, as well as 1, 4, and 7 days. Results: Both CW and WW delayed burn progression without reducing the final burn Departmenth (deep dermis). In contrast, only WW but not CW increased dermal perfusion (81 ± 2% (WW) vs. 62 ± 2% (CW) and 63 ± 1% (CON), p< 0·05) already 1 hour after burn induction. The difference observed after one hour led to a complete flow recovery during the observation period and translated into increased interspace survival, respectively less necrosis with WW(65 ± 4% vs. 81 + 4% (CW) and 91 ± 2% (CON), p< 0·05) after 7 days. Conclusions: Application of warm water significantly improved dermal perfusion, increased interspace survival, and delayed burn progression.However it didn't alter the ultimate burn Departmenth of the actually burned area. Therefore, warm water can create a therapeutic window for targeted nonsurgical treatment of burn progression.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.

BACKGROUND AND PURPOSE: Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. METHODS: In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. RESULTS: One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5-2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0-5.0) compared with 7.9% (95% confidence interval, 7.2-8.7) in ischemic strokes. CONCLUSIONS: In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

Parésie trochléaire transitoire comme signe neurologique inaugural d'une panartérite noueuse [Transient trochlear nerve palsy as the presenting neurological sign of panarteritis nodosa]

INTRODUCTION: Panarteritis nodosa (PAN) is a systemic vasculitis affecting small and medium-sized arteries. Neuro-ophthalmological complications of PAN are rare but numerous, and may affect the eye, the visual and the oculomotor pathways. Such complications occur mainly in patients previously diagnosed with PAN. OBSERVATION: A 51-year-old woman presented with an isolated right trochlear (IV) palsy, in the setting of headaches and fluctuating fever of unknown etiology. Erythrocyte sedimentation rate was 13 mm and full blood cell count was normal. Previous chest X-ray and blood studies were negative for an infection or inflammation. Orbital and cerebral CT scan was normal. Spontaneous recovery of diplopia ensued over four days. Two days later, paresthesia and sensory paresis of the dorsal portion of the left foot were present. Lumbar puncture revealed 14 leucocytes (76 percent lymphocytes) with elevated proteins, but blood studies and serologies were negative. A diagnosis of undetermined meningo-myelo-radiculoneuritis was made. Because of a possible tick bite six weeks previously the patient was empirically treated with 2 g intravenous ceftriaxone for 3 weeks. Fever rapidly dropped. Six weeks after the onset of diplopia, acute onset of blindness in her right eye, diffuse arthralgias and fever motivated a new hospitalization. There was a central retinal artery occlusion of the right eye. Blood studies now revealed signs of systemic inflammation (ESR 30 mm, CRP 12 mg/L, ANA 1/80, pANCA 1/40, leucocytosis 12.4 G/L, Hb 111 g/L, Ht 33 percent). Biopsy of the left sural nerve revealed arterial fibrinoid necrosis. A diagnosis of PAN was made. CONCLUSIONS: Transient diplopia can be the heralding symptom of a systemic vasculitis such as PAN, giant cell arteritis and Wegener granulomatosis. In this patient the presence of accompanying systemic symptoms raised a suspicion of systemic inflammation, but the absence of serologic and imaging abnormalities precluded a specific diagnosis initially. A few weeks later, the presence of a second ischemic event (retinal) and positive blood studies led to a further diagnostic procedure. Oculomotor and abducens palsies have rarely been reported in association with PAN. We report the first case of trochlear nerve paresis as the inaugural neurological sign of PAN. This case highlights the importance of considering inflammatory systemic disorders in patients with acute diplopia particularly when they are young, lack vascular risk factors or cause, and complain of associated systemic symptoms.

Changes in cerebral compartmental compliances during mild hypocapnia in patients with traumatic brain injury.

The benefit of induced hyperventilation for intracranial pressure (ICP) control after severe traumatic brain injury (TBI) is controversial. In this study, we investigated the impact of early and sustained hyperventilation on compliances of the cerebral arteries and of the cerebrospinal (CSF) compartment during mild hyperventilation in severe TBI patients. We included 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom an increase in ventilation (20% increase in respiratory minute volume) was performed during 50 min as part of a standard clinical CO(2) reactivity test. Using a new mathematical model, cerebral arterial compliance (Ca) and CSF compartment compliance (Ci) were calculated based on the analysis of ICP, arterial blood pressure, and cerebral blood flow velocity waveforms. Hyperventilation initially induced a reduction in ICP (17.5 ± 6.6 vs. 13.9 ± 6.2 mmHg; p < 0.001), which correlated with an increase in Ci (r(2) = 0.213; p = 0.015). Concomitantly, the reduction in cerebral blood flow velocities (CBFV, 74.6 ± 27.0 vs. 62.9 ± 22.9 cm/sec; p < 0.001) marginally correlated with the reduction in Ca (r(2) = 0.209; p = 0.017). During sustained hyperventilation, ICP increased (13.9 ± 6.2 vs. 15.3 ± 6.4 mmHg; p < 0.001), which correlated with a reduction in Ci (r(2) = 0.297; p = 0.003), but no significant changes in Ca were found during that period. The early reduction in Ca persisted irrespective of the duration of hyperventilation, which may contribute to the lack of clinical benefit of hyperventilation after TBI. Further studies are needed to determine whether monitoring of arterial and CSF compartment compliances may detect and prevent an adverse ischemic event during hyperventilation.

Neurodevelopmental outcome of neonates treated with nitric oxide for persistent pulmonary hypertension

Persistent pulmonary hypertension of the newborn (PPHN) is a life threatening condition associated with an increased risk of neurodevelopmental impairment. The recommended treatment for this condition is inhaled nitric oxide (iNO) and has been used in our Neonatal Intensive Care Unit since 1998. We prospectively offered neurodevelopmental follow-up to children treated with iNO for PPHN, including extensive neurological evaluation, developmental/cognitive evaluation at 18 months and 3.5-5 years old, and evaluated the rate of severe and moderate handicap and normal neurodevelopmental outcome, compared to a control group and the literature. Population consisted of 29 patients treated only with iNO, born between 01.01.1999 and 31.12.2005 (study group), and 32 healthy term infants born in 1998 in our maternity (control group). During those seven years, 65 infants were admitted in our Unit with PPHN, of whom 40 were treated with iNO alone. 34 children survived (85%) and were offered neurodevelopmental follow-up, 7 children were lost to follow-up due to various reasons. 22 children were examined at the age of 18 months (76%) with a rate of moderate handicap of 22% (2 with expressive language delay, 2 with difficult behavior, and 1 child with moderate hearing loss), and a rate of major handicap of 4.5% (1 child with cerebral palsy due to perinatal stroke, and moderate hearing loss). At preschool age, 17 (50%) were examined, the rate of moderate handicap was 22% (4 borderline intelligence, 1 hearing loss), and the rate of major handicap was 4.5% (one child with cerebral palsy and hearing loss), compared to 26.9% and 0% in the control group. Mean developmental quotient at 18 months was 100.3 ± 8.7 (control group 118.3), and at preschool age mean cognitive indices were within normal limits for the 2 tests performed at 3.5 or 5 years (108 ± 21, 94.4 ± 17). Most of the children with a less favorable neurodevelopmental outcome suffered from birth asphyxia (ruptured uterus, placental abruption, maternal hypotension, diabetic cardiomyopathy), and notably, the 2 children with sensorineural hearing loss both suffered from severe hypoxic-ischemic enkelopathy. Treatment with iNO was not the direct cause of the neurodevelopmental impairments observed in children treated for PPHN.

Scleritis after proton therapy in uveal melanoma [Skleritis nach Protonentherapie bei Aderhautmelanom]

BACKGROUND: Sclera is a very radioresistant tissue and scleritis after proton therapy has not been described so far. HISTORY AND SIGNS: Four female patients, aged between 31 and 74 years, were treated with proton therapy for uveal melanoma (height range: 2.2 - 3.5 mm), located in the macula, the superior equator and 2 in the ciliary body. All patients had a history of a previous or active inflammatory disease and developed scleritis after radiotherapy. THERAPY AND OUTCOME: Two patients had infectious scleritis and were treated with adequate antibiotic therapy. After systemic corticotherapy, 3 patients recovered completely; the remaining patient was managed with additional immunosuppressive treatment as well as a conjunctival and scleral graft, but has not become pain free yet. CONCLUSION: Scleritis is a possible complication after proton therapy, probably on an ischemic basis, where there is a predisposing factor such as inflammatory systemic disease.

Une cause de cardiomyopathie dilatée chez l'enfant: le déficit primaire en carnitine [A cause of dilated cardiomyopathy in child: primary carnitine deficiency].

AIM: The aim of this case report was to show the importance to research metabolic etiology, especially a carnitine deficiency in dilated cardiomyopathy of children. CASE REPORT: A three years old Togolese child presented muscular hypotonia, dyspnea. Examination showed left galop murmur and systolic murmur 2/6. Chest X-ray showed cardiomegaly (CTI: 0.66), electrocardiogram, a sinusal rythm, left ventricle hypertrophy and T wave abnormalities. Echocardiogram showed a markedly dilated left ventricle with reduced systolic function (EF: 0.43; reference range 0.55-0.80) and moderate mitral regurgitation. The inflammatory signs where negatives. Magnetic resonance imaging don't show signs of ischemic or myocarditis. The levels of free and total plasmatic carnitine decreased: 3μmol/L (N: 18-48μmol/L) and 5μmol/l (N: 29-70μmol/L) respectively. Mutation analysis of the gene SLC22A5 confirms the diagnosis of primary systemic carnitine deficiency. Treatment with oral carnitine was started at 200mg/kg per day. Within three weeks of treatment, we observed the decrease of all symptoms and the left ventricular size and function normalized (EF: 0.62). He has now been on oral carnitine for live. CONCLUSION: Primary carnitine deficiency is a cause of dilated cardiomyopathy in child. It must systematically be suspected when a child presents a primitive cardiomyopathy. The treatment with oral carnitine for live is simple, with excellent prognosis.

Excitotoxicity-induced endocytosis confers drug targeting in cerebral ischemia.

OBJECTIVE: Targeting neuroprotectants specifically to the cells that need them is a major goal in biomedical research. Many peptidic protectants contain an active sequence linked to a carrier such as the transactivator of transcription (TAT) transduction sequence, and here we test the hypothesis that TAT-linked peptides are selectively endocytosed into neurons stressed by excitotoxicity and focal cerebral ischemia. METHODS: In vivo experiments involved intracerebroventricular injection of TAT peptides or conventional tracers (peroxidase, fluorescein isothiocyanate-dextran) in young rats exposed to occlusion of the middle cerebral artery at postnatal day 12. Cellular mechanisms of uptake were analyzed in dissociated cortical neuronal cultures. RESULTS: In both models, all tracers were taken up selectively into stressed neurons by endocytosis. In the in vivo model, this was neuron specific and limited to the ischemic area, where the neurons displayed enhanced immunolabeling for early endosomal antigen-1 and clathrin. The highly efficient uptake of TAT peptides occurred by the same selective mechanism as for conventional tracers. All tracers were targeted to the nucleus and cytoplasm of neurons that appeared viable, although ultimately destined to die. In dissociated cortical neuronal cultures, an excitotoxic dose of N-methyl-D-aspartate induced a similar endocytosis. It was 100 times more efficient with TAT peptides than with dextran, because the former bound to heparan sulfate proteoglycans at the cell surface, but it depended on dynamin and clathrin in both cases. INTERPRETATION: Excitotoxicity-induced endocytosis is the main entry route for protective TAT peptides and targets selectively the neurons that need to be protected.

CT angiography helps to differentiate acute from chronic carotid occlusion: "carotid ring sign".

INTRODUCTION: Currently, there is no reliable method to differentiate acute from chronic carotid occlusion. We propose a novel CTA-based method to differentiate acute from chronic carotid occlusions that could potentially aid clinical management of patients. METHODS: We examined 72 patients with 89 spontaneously occluded extracranial internal carotids with CT angiography (CTA). All occlusions were confirmed by another imaging modality and classified as acute (imaging <1 week of presumed occlusion) orchronic (imaging >4 weeks), based on circumstantial clinical and radiological evidence. A neuroradiologist and a neurologist blinded to clinical information determined the site of occlusion on axial sections of CTA. They also looked for (a) hypodensity in the carotid artery (thrombus), (b) contrast within the carotid wall (vasa vasorum), (c) the site of the occluded carotid, and (d) the "carotid ring sign" (defined as presence of a and/or b). RESULTS: Of 89 occluded carotids, 24 were excluded because of insufficient circumstantial evidence to determine timing of occlusion, 4 because of insufficient image quality, and 3 because of subacute timing of occlusion. Among the remaining 45 acute and 13 chronic occlusions, inter-rater agreement (kappa) for the site of proximal occlusion was 0.88, 0.45 for distal occlusion, 0.78 for luminal hypodensity, 0.82 for wall contrast, and 0.90 for carotid ring sign. The carotid ring sign had 88.9% sensitivity, 69.2% specificity, and 84.5% accuracy to diagnose acute occlusion. CONCLUSION: The carotid ring sign helps to differentiate acute from chronic carotid occlusion. If further confirmed, this information may be helpful in studying ischemic symptoms and selecting treatment strategies in patients with carotid occlusions.

Prise en charge des sténoses carotidiennes [Management of the carotid artery stenosis].

In the western world, the carotid-artery stenosis is one of the major causes of ischemic stroke in elderly people. The principal therapeutic indication is a symptomatic stenosis > 50% in the first two weeks and the surgical approach has shown the best results. Despite inferior results to carotid endarterectomy in terms of post-operative rate of stroke and/or death, except for young patients, carotid stenting remains the best choice in patients at high surgical risk. The best medical treatment, consisting in correction of cardiovascular risk factors, statin therapy and anti-aggregation led to a drastic reduction in the annual rate of stroke associated to carotid stenosis and thus limited the surgical intervention in asymptomatic patient to men with a life expectancy of at least 5 years and a stenosis > 70%.

Neurologie [Therapeutic advances in neurology].

The neurology field has been greatly improved in 2008. The therapeutic window of intravenous thrombolysis for acute ischemic stoke is extended to 4 h 30. New studies show that the clinical progression of Parkinson's disease might be slowed by some medication. Deep brain stimulation may be beneficial early in the course of the disease. Tysabri and Fingolimod in multiple sclerosis are discussed. The pharmacopoeia for epilepsy is in constant development with new products recently released in Switzerland. CGRP receptor antagonists are about to be launched as a promising acute migraine treatment. The pharmacological approach in amyotrophic lateral sclerosis patients might be improved according to research results.

Prediction of Recanalization Trumps Prediction of Tissue Fate: The Penumbra: A Dual-edged Sword.

BACKGROUND AND PURPOSE: To determine whether infarct core or penumbra is the more significant predictor of outcome in acute ischemic stroke, and whether the results are affected by the statistical method used. METHODS: Clinical and imaging data were collected in 165 patients with acute ischemic stroke. We reviewed the noncontrast head computed tomography (CT) to determine the Alberta Score Program Early CT score and assess for hyperdense middle cerebral artery. We reviewed CT-angiogram for site of occlusion and collateral flow score. From perfusion-CT, we calculated the volumes of infarct core and ischemic penumbra. Recanalization status was assessed on early follow-up imaging. Clinical data included age, several time points, National Institutes of Health Stroke Scale at admission, treatment type, and modified Rankin score at 90 days. Two multivariate regression analyses were conducted to determine which variables predicted outcome best. In the first analysis, we did not include recanalization status among the potential predicting variables. In the second, we included recanalization status and its interaction between perfusion-CT variables. RESULTS: Among the 165 study patients, 76 had a good outcome (modified Rankin score ≤2) and 89 had a poor outcome (modified Rankin score >2). In our first analysis, the most important predictors were age (P<0.001) and National Institutes of Health Stroke Scale at admission (P=0.001). The imaging variables were not important predictors of outcome (P>0.05). In the second analysis, when the recanalization status and its interaction with perfusion-CT variables were included, recanalization status and perfusion-CT penumbra volume became the significant predictors (P<0.001). CONCLUSIONS: Imaging prediction of tissue fate, more specifically imaging of the ischemic penumbra, matters only if recanalization can also be predicted.