Cerebral Sinovenous Thrombosis in Children: Clinical Presentation and Extension, Localization and Recanalization of Thrombosis

Many important questions regarding pathophysiology and treatment of cerebral sinovenous thrombosis need clarification and may depend on further knowledge on the etiology, site, extension and recanalization of the thrombosis. We studied these variables in a cohort of children and adolescents from seven Portuguese Centers. We conclude from our results that the deep venous system and the superior longitudinal sinus are less frequently affected with thrombosis but have a greater potential for serious neurologic disease and for major sequelae. Non-recanalization, at least in the long term, is not an adverse prognostic factor. Extensive propagation of the thrombus from the initial site of origin seems to be common. The early identification of risk factors and their treatment coupled with an aggressive attitude towards diagnosis and treatment for thrombosis involving the deep venous system would be warranted.

Relação entre Hipotiroidismo Subclínico e Doença Coronária: um Estudo com Angiografia

INTRODUCTION: The definition of subclinical hypothyroidism (SH) is an asymptomatic state in which free thyroxine (T4) is normal and thyroid-stimulating hormone (TSH) levels are elevated. Its relationship with coronary disease is not clear and has been the subject of recent interest. Current evidence is conflicting and there is a lack of studies supported by coronary angiography. OBJECTIVE: To assess the relationship between SH and the presence and extent of coronary disease diagnosed by angiography. METHODS: We prospectively studied 354 consecutive patients referred for elective coronary angiography. Those with known thyroid disease, documented coronary disease or previous myocardial infarction were excluded. Fasting blood specimens were collected to measure thyroid hormones, lipid profile, high-sensitivity C-reactive protein, fibrinogen and NT-proBNP. Patients with SH were compared with those without to assess differences in clinical characteristics and biochemical and angiographic results. Significant coronary disease was defined as the presence of at least one lesion with > or = 50% luminal stenosis. Lesions with <50% stenosis were considered minimal. RESULTS: SH was diagnosed in 32 (9%) patients. Mean age was similar between the groups. There were more women (66% vs. 39%; p=0.003) and atrial fibrillation was more frequent (25% vs. 11%; p=0.016) in the group of patients with SH. There were no significant differences in the other baseline clinical parameters, and blood biochemistry results were similar in the two groups, with the exception of higher levels of NT-proBNP in SH patients, although without statistical significance. The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064). CONCLUSION: In this population SH was not associated with the presence or extent of coronary disease diagnosed by coronary angiography.

A Rare Variation of the Extensor Indicis Proprius Tendon With Important Clinical Implications

Introduction: Anatomical variations of the extensor tendons to the fingers are of great clinical interest, due to the relatively high frequency of tendon injury in clinical practice. Material and methods: During routine dissection of the right upper limb of a 67-year-old female preserved corpse, the extensor indicis proprius (EIP) muscle belly originated 3 independent tendons, each with a separate fascial sheath, forming a triple EIP tendon. There was a larger tendon, which occupied a central position, that represented the usual single EIP tendon. In addition, there were two thinner radial and ulnar accessory EIP tendons. The radial-EIP tendon crossed deep to the extensor digitorum communis (EDC) tendon to the index finger in the distal half of the dorsum of the hand to reach the radial side of the extensor expansion hood of the index finger. Discussion: According to the literature, the frequency of a triple EIP tendon ranges from 0%, to as high as 7%, although most authors do not acknowledge the presence of this variant in their series. This variant of the EIP tendon, in which the radial-EIP terminated laterally to the termination of the tendon of the EDC to the index finger, may be a source of confusion intraoperatively, as the EIP tendon has traditionally been identified on the basis of its ulnar location with respect to the EDC tendon. Conclusion: The possibility of a triple EIP tendon should certainly be born in mind by all surgeons when performing tendon repairs, tenoplasties or tendon transfers.

Intraepidermal Epidermotropic Metastatic Melanoma: a Clinical and Histopathological Mimicker of Melanoma in Situ Occurring in Multiplicity

The distinction between primary melanoma and melanoma metastatic to the skin has major prognostic implications. We report a case of a 67-year-old male with a diagnosis of a superficial spreading melanoma (stage IB) rendered 6 years earlier who presented clinically with an atypical nevus on his left thigh. Histopathological examination showed an intraepidermal melanocytic proliferation that was interpreted as melanoma in situ. Subsequently, 45 additional pigmented macules appeared in crops over a 9-month period. Clinically and dermoscopically, these lesions were extremely polymorphic. Histopathological findings were compatible with melanoma in situ, as each lesion consisted of a wholly intraepidermal proliferation of markedly atypical melanocytes arranged singly and in nests. A complete gastrointestinal study showed multiple pigmented metastatic lesions throughout the stomach and small bowel, which supported a diagnosis of metastatic melanoma with gastrointestinal and epidermotropic skin involvement. Monosomy of chromosome 9 and a BRAF V600E mutation were detected in the primary tumor sample and in macro-dissected secondary lesions. No CDKN2A or CDK4 germline mutations were found. Intraepidermal epidermotropic metastases of melanoma have been rarely described in literature. In this case, histopathology alone was insufficient to distinguish metastatic melanoma from multiple in situ melanomas. The recognition of epidermotropic metastases should be based on the correlation between clinical, dermoscopic, histopathological and molecular findings.

Clinical and Bacteriological Survey of Diabetic Foot Infections in Lisbon

AIMS: An epidemiological survey of diabetic foot infections (DFIs) in Lisbon, stratifying the bacterial profile based on patient demographical data, diabetic foot characteristics (PEDIS classification), ulcer duration and antibiotic therapy. METHODS: A transversal observational multicenter study, with clinical data collection using a structured questionnaire and microbiological products (aspirates, biopsies or swabs collected using the Levine method) of clinically infected foot ulcers of patients with diabetes mellitus (DM). RESULTS: Forty-nine hospitalized and ambulatory patients were enrolled in this study, and 147 microbial isolates were cultured. Staphylococcus was the main genus identified, and methicillin-resistant Staphylococcus aureus (MRSA) was present in 24.5% of total cases. In the clinical samples collected from patients undergoing antibiotic therapy, 93% of the antibiotic regimens were considered inadequate based on the antibiotic susceptibility test results. The average duration of an ulcer with any isolated multi-drug resistant (MDR) organism was 29 days, and previous treatment with fluoroquinolones was statistically associated with multi-drug resistance. CONCLUSIONS: Staphylococcus aureus was the most common cause of DFIs in our area. Prevalence and precocity of MDR organisms, namely MRSA, were high and were probably related to previous indiscriminate antibiotic use. Clinicians should avoid fluoroquinolones and more frequently consider the use of empirical anti-MRSA therapy.

Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease.

A Rare Variant of the Ulnar Artery with Important Clinical Implications: a Case Report

BACKGROUND: Variations in the major arteries of the upper limb are estimated to be present in up to one fifth of people, and may have significant clinical implications. CASE PRESENTATION: During routine cadaveric dissection of a 69-year-old fresh female cadaver, a superficial brachioulnar artery with an aberrant path was found bilaterally. The superficial brachioulnar artery originated at midarm level from the brachial artery, pierced the brachial fascia immediately proximal to the elbow, crossed superficial to the muscles that originated from the medial epicondyle, and ran over the pronator teres muscle in a doubling of the antebrachial fascia. It then dipped into the forearm fascia, in the gap between the flexor carpi radialis and the palmaris longus. Subsequently, it ran deep to the palmaris longus muscle belly, and superficially to the flexor digitorum superficialis muscle, reaching the gap between the latter and the flexor carpi ulnaris muscle, where it assumed is usual position lateral to the ulnar nerve. CONCLUSION: As far as the authors could determine, this variant of the superficial brachioulnar artery has only been described twice before in the literature. The existence of such a variant is of particular clinical significance, as these arteries are more susceptible to trauma, and can be easily confused with superficial veins during medical and surgical procedures, potentially leading to iatrogenic distal limb ischemia.

Clinical Outcome and Morphologic Analysis after Endovascular Aneurysm Repair Using the Excluder Endograft

OBJECTIVE: Long-term follow-up after endovascular aneurysm repair (EVAR) is very scarce, and doubt remains regarding the durability of these procedures. We designed a retrospective cohort study to assess long-term clinical outcome and morphologic changes in patients with abdominal aortic aneurysms (AAAs) treated by EVAR using the Excluder endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz). METHODS: From 2000 to 2007, 179 patients underwent EVAR in a tertiary institution. Clinical data were retrieved from a prospective database. All patients treated with the Excluder endoprosthesis were included. Computed tomography angiography (CTA) scans were retrospectively analyzed preoperatively, at 30 days, and at the last follow-up using dedicated tridimensional reconstruction software. For patients with complications, all remaining CTAs were also analyzed. The primary end point was clinical success. Secondary end points were freedom from reintervention, sac growth, types I and III endoleak, migration, conversion to open repair, and AAA-related death or rupture. Neck dilatation, renal function, and overall survival were also analyzed. RESULTS: Included were 144 patients (88.2% men; mean age, 71.6 years). Aneurysms were ruptured in 4.9%. American Society of Anesthesiologists classification was III/IV in 61.8%. No patients were lost during a median follow-up of 5.0 years (interquartile range, 3.1-6.4; maximum, 11.2 years). Two patients died of medical complications ≤ 30 days after EVAR. The estimated primary clinical success rates at 5 and 10 years were 63.5% and 41.1%, and secondary clinical success rates were 78.3% and 58.3%, respectively. Sac growth was observed in 37 of 142 patients (26.1%). Cox regression showed type I endoleak during follow-up (hazard ratio, 3.74; P = .008), original design model (hazard ratio, 3.85; P = .001), and preoperative neck diameter (1.27 per mm increase, P = .006) were determinants of sac growth. Secondary interventions were required in 32 patients (22.5%). The estimated 10-year rate of AAA-related death or rupture was 2.1%. Overall life expectancy after AAA repair was 6.8 years. CONCLUSIONS: EVAR using the Excluder endoprosthesis provides a safe and lasting treatment for AAA, despite the need for maintained surveillance and secondary interventions. At up to 11 years, the risk of AAA-related death or postimplantation rupture is remarkably low. The incidences of postimplantation sac growth and secondary intervention were greatly reduced after the introduction of the low-permeability design in 2004.

Postmenopausal Bleeding and Endometrial Changes: Clinical Significance?

Introduction: Postmenopausal bleeding is a common complaint from women seen in general practice, although majority of them, will have no major problem. Objective: Study of endometrium in postmenopausal women with suspicious sonographic endometrial changes. Comparison of findings in asymptomatic women and those who reported metrorrhagia. Methods: Consultation of outpatient medical records of 487 women undergoing endometrial study (sonohysterography, hysteroscopy), between January/2004 and July/2010. Patients were subdivided into two groups: women with (G1) and without (G2) complaints of postmenopausal metrorrhagia. Results: G1 and G2 comprises 78 and 409 women, respectively. G1: 23.1% normal uterine cavity, 74.3% benign pathology (majority endometrial polyps) and 2.6% of them endometrial carcinoma. G2: 14.4% normal uterine cavity, 83.7% benign pathology (majority endometrial polyps), 1.4% endometrial hyperplasia and endometrial carcinoma in 0.49%. Conclusion: Postmenopausal metrorrhagia is associated with an increased risk of endometrial malignancy, in relation to asymptomatic, although represents a minority of the population. To highlight the existence of premalignant and malignant pathology in asymptomatic endometrial thickening.

Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance

Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction. Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies. Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ≥ 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating alloantibodies were absent in 92.5% of the C4d negative biopsies. Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies. The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%).

Demographic and Clinical Characteristics of Human Immunodeficiency Virus-Infected Patients Receiving Dialysis in Portugal: a Nationwide Multicentre Survey

Background: Data on human immunodeficiency virus (HIV) infected patients receiving dialysis in Portugal is scarce. Methods: This nationwide epidemiological survey retrospectively evaluates HIV-infected patients on chronic dialysis in Portugal between 1997 and 2002. Results: Sixty-six patients were evaluated (mean age: 39.1±1.6 years, 47 men, 35 black African). Sixty-two patients started dialysis and 4 patients who were receiving dialysis had HIV seroconversion. Eighty-five percent of patients were treated in Lisbon. The annual incidence of HIV-infected patients on chronic dialysis was 0.5% in 1997 and 0.9% in 2002. Seventy-eight percent of patients were HIV-1 infected , 13% had hepatitis B and 31% hepatitis C. Sexual contact was the mode of transmission of HIV in 53% of cases. Four patients had biopsy-proved HIV-associated nephropathy. Ninety-five percent of patients were on chronic hemodialysis. Fifty percent of patients had acquired immunodeficiency syndrome. At follow-up, 12 patients died. HIV-infected CKD patient survival after starting dialysis was 80% at 3 years. Conclusion: The incidence of HIV-infected patients on chronic dialysis in Portugal has almost doubled. Widespread use of highly active antiretroviral therapy and the increasing number of black Africans from former overseas Portuguese colonies now living in Portugal are possible reasons for this large increase.

TINU syndrome – Two Clinical Cases of Tubulo-Interstitial Nephritis and Uveitis

TINU (Tubulo-Interstitial Nephritis and Uveitis)syndrome is a rare disease of unknown aetiology characterised by the association between interstitial nephritis and uveitis. The authors present the cases of two young children whose symptoms began with anorexia and weight loss, associated with renal failure and proteinuria of tubular origin. One child also presented anaemia, glycosuria without hyperglycaemia and microhaematuria. A few months later both developed uveitis. In both cases the renal biopsy showed changes compatible with interstitial nephritis. As interstitial nephritis and uveitis aetiologies were not identified, TINU syndrome was suggested as a possible diagnosis. In both children there was a complete resolution, with one needing systemic steroids and immunosuppressive treatment. TINU syndrome should always be considered in the differential diagnosis of patients with renal and ophthalmologic changes.

Clinical Dilemma in the Treatment of a Patient with Microangiopathic Haemolytic Anaemia, Thrombocytopaenia and Severe Hypertension

While haemolytic uraemic syndrome in children is predominantly associated with Shiga toxin -producing Escherichia coli (typically 0157:H7), some cases occur without associated diarrhoea, or as the manifestation of an underlying disorder other than infection. Haemolytic uraemic syndrome is characterised by microangiopathic anaemia, thrombocytopaenia and renal failure, on occasion accompanied by severe hypertension. Malignant hypertension is a syndrome that sometimes exhibits the same laboratory abnormalities as haemolytic uraemic syndrome as it may share the same pathological findings: thrombotic microangiopathy. As clinical features of both entities overlap, the distinction between them can be very difficult. However, differentiation is essential for the treatment decision, since early plasma exchange dramatically reduces mortality in haemolytic uraemic syndrome not associated with diarrhoea. An increasing number of genetic causes of this pathology have been described and may be very useful in differentiating it from thrombotic microangiopathy due to other aetiologies. Despite advances in the understanding of the pathophysiology of haemolytic uraemic syndrome not associated with diarrhoea, the management often remains empirical. We describe a patient with simultaneous microangiopathic haemolytic anaemia, thrombocytopaenia and severe hypertension managed in the acute period of illness with plasma exchange.

Oral Contraceptive Use and Clinical Outcomes in Patients with Multiple Sclerosis

Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002, respectively). These patients were also more likely to have a benign disease course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p<0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for MSSS β: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course.

Predicting Outcome after Cardiopulmonary Arrest in Therapeutic Hypothermia Patients: Clinical, Electrophysiological and Imaging Prognosticators

INTRODUCTION: Predicting outcome in comatose survivors of cardiac arrest is based on data validated by guidelines that were established before the era of therapeutic hypothermia. We sought to evaluate the predictive value of clinical, electrophysiological and imaging data on patients submitted to therapeutic hypothermia. MATERIALS AND METHODS: A retrospective analysis of consecutive patients receiving therapeutic hypothermia during years 2010 and 2011 was made. Neurological examination, somatosensory evoked potentials, auditory evoked potentials, electroencephalography and brain magnetic resonance imaging were obtained during the first 72 hours. Glasgow Outcome Scale at 6 months, dichotomized into bad outcome (grades 1 and 2) and good outcome (grades 3, 4 and 5), was defined as the primary outcome. RESULTS: A total of 26 patients were studied. Absent pupillary light reflex, absent corneal and oculocephalic reflexes, absent N20 responses on evoked potentials and myoclonic status epilepticus showed no false-positives in predicting bad outcome. A malignant electroencephalographic pattern was also associated with a bad outcome (p = 0.05), with no false-positives. Two patients with a good outcome showed motor responses no better than extension (false-positive rate of 25%, p = 0.008) within 72 hours, both of them requiring prolonged sedation. Imaging findings of brain ischemia did not correlate with outcome. DISCUSSION: Absent pupillary, corneal and oculocephalic reflexes, absent N20 responses and a malignant electroencephalographic pattern all remain accurate predictors of poor outcome in cardiac arrest patients submitted to therapeutic hypothermia. CONCLUSION: Prolonged sedation beyond the hypothermia period may confound prediction strength of motor responses.