Restless Legs Syndrome in NKX2-1-related chorea: An expansion of the disease spectrum.

BACKGROUND: Molecular technologies are expanding our knowledge about genetic variability underlying early-onset non-progressive choreic syndromes. Focusing on NKX2-1-related chorea, the clinical phenotype and sleep related disorders have been only partially characterized. METHODS: We propose a retrospective and longitudinal observational study in 7 patients with non-progressive chorea due to NKX2-1 mutations. In all subjects sleep and awake EEG, brain MRI with study of pituitary gland, chest X-rays, endocrinological investigations were performed. Movement disorders, pattern of sleep and related disorders were investigated using structured clinical evaluation and several validated questionnaires. RESULTS: In patients carrying NKX2-1 mutations, chorea was mainly distributed in the upper limbs and tended to improve with age. All patients presented clinical or subclinical hypothyroidism and delayed motor milestones. Three subjects had symptoms consistent with Restless Legs Syndrome (RLS) that improved with Levodopa. CONCLUSIONS: Patients with NKX2-1 gene mutations should be investigated for RLS, which, similarly to chorea, can sometimes be ameliorated by Levodopa.

Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome.

Background Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta during pregnancy and theoretically reach the fetal brain. Some studies showed an increased number of learning disabilities in these children. Objectives To evaluate the long-term neurodevelopmental outcome of 40 children (median age 7.4 years) born to mothers with SLE and/or APS carrying positive IgG aPL during the third trimester of pregnancy. Methods Children were checked for neurological physical exam and intellectual/cognitive functioning by the Wechsler scale for corrected age. We submitted to the mothers the Child Behavior CheckList (CBCL) and a homemade set of questions created by pediatric neurologists. Results In all children neurological physical exam and intelligence levels were found to be normal. A cognitive impairment or a discrepant cognitive profile was found in 3 (7%) and 11 (28%) children, respectively. Learning disabilities were diagnosed in 3 children (19% of school-age children), all born to mothers with triple aPL positivity. A history of epilepsy was shown in four children (10%). CONCLUSIONS: Children born to women with SLE and/or APS may need a long-term follow-up focusing on milestones of neurodevelopment in order to detect and correct any alteration as early as possible.

Children born to SLE and APS mothers.

BACKGROUND: Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Pregnancies in these patients carry several complications such as prematurity. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta but they don't generally cause any neonatal thrombotic event. Because of the incompleteness of the fetal blood-brain barrier, aPL could theoretically reach the fetal brain. Whether this can have an effect on brain development is still under investigation. Some studies performed in children of patients with SLE and/or APS showed an increased number of learning disabilities without impairment in intelligence level. OBJECTIVES: The objectives of this article are to evaluate the neurodevelopment outcome in 30 children (median age 9 years) born to mothers with SLE and/or APS with IgG anti-beta2-glycoprotein I during the third trimester of pregnancy and found positive for the same antibodies at birth. METHODS: A neurological physical exam was performed in all children. We submitted some questionnaires to the mothers: the Child Behavior CheckList (CBCL) and a homemade set of questions obtained by a team composed of rheumatologists and pediatric neurologists. Intellectual functioning was determined by the Wechsler scale for corrected age. RESULTS: In all children neurological physical exam and intelligence levels were found to be normal but mild behavior disorders and history of neurological manifestations were shown in three children. CONCLUSIONS: Offspring of patients with SLE and/or APS are generally healthy. We and others observed the occurrence of minor neurological disorders that might be related to maternal disease or to prematurity. The limited number of the available data on this sensitive issue supports the need for further studies.

The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that primarily affects women of childbearing-age. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by the occurrence of venous and arterial thrombosis, often multiple, and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Recently, the long-term outcome of children born to patients with lupus and APS has become a major topic of interest both to patients and physicians. One of the major problems related to maternal disease is preterm delivery with all the consequences that this condition may bring. Prematurity may also be due to the presence of aPL; however, aPL do not generally display any thrombotic potential on neonates. Another complication may be neonatal lupus (NL), mediated by the presence of maternal antibodies (anti-Ro/SSA and anti-La/SSB). In addition, behaviour and neuropsychological outcomes have also been a matter of interest, but there are currently few data available. Beyond the biological influence of both maternal disease and autoimmune background, it is important to focus on the possible influence of maternal chronic illness on the neuropsychological development of her children. Whether aPL exposure could have a direct effect on brain development is still being debated. In children of mothers with APS, language delays have been noted and learning disabilities were described with a higher rate than the general age-school population. Several studies were performed on children born to lupus mothers: even if maternal lupus does not seem to impair intelligence levels, it may increase the occurrence of learning disabilities and particularly dyslexia in male children. To the best of our knowledge, no studies are available on the long-term outcome of children born to mothers with lupus or APS and particularly regarding the development of autoimmune diseases. Nevertheless, common experience of experts in the field is that these children do not show a significantly increased risk of displaying the same autoimmune disease as their mothers. The purpose of this paper is to answer the frequently asked questions of patients with lupus and APS who desire to become mothers, based on the little information available.

A comprehensive approach to long-standing facial paralysis based on lengthening temporalis myoplasty.

Long-standing peripheral monolateral facial paralysis in the adult has challenged otolaryngologists, neurologists and plastic surgeons for centuries. Notwithstanding, the ultimate goal of normality of the paralyzed hemi-face with symmetry at rest, and the achievement of a spontaneous symmetrical smile with corneal protection, has not been fully reached. At the beginning of the 20(th) century, the main options were neural reconstructions including accessory to facial nerve transfer and hypoglossal to facial nerve crossover. In the first half of the 20(th) century, various techniques for static correction with autologous temporalis muscle and fascia grafts were proposed as the techniques of Gillies (1934) and McLaughlin (1949). Cross-facial nerve grafts have been performed since the beginning of the 1970s often with the attempt to transplant free-muscle to restore active movements. However, these transplants were non-vascularized, and further evaluations revealed central fibrosis and minimal return of function. A major step was taken in the second half of the 1970s, with the introduction of microneurovascular muscle transfer in facial reanimation, which, often combined in two steps with a cross-facial nerve graft, has become the most popular option for the comprehensive treatment of long-standing facial paralysis. In the second half of the 1990s in France, a regional muscle transfer technique with the definite advantages of being one-step, technically easier and relatively fast, namely lengthening temporalis myoplasty, acquired popularity and consensus among surgeons treating facial paralysis. A total of 111 patients with facial paralysis were treated in Caen between 1997 and 2005 by a single surgeon who developed 2 variants of the technique (V1, V2), each with its advantages and disadvantages, but both based on the same anatomo-functional background and aim, which is transfer of the temporalis muscle tendon on the coronoid process to the lips. For a comprehensive treatment of the paralysis, the eyelids are usually managed by Paul Tessier's technique to lengthen the levator muscle of the upper eyelid by aponeurosis interposition, combined with external blepharorrhaphy with Krastinova-Lolov's technique. Facial reanimation using lengthening temporalis myoplasty is a dynamic procedure that has its roots in the techniques of Gillies and McLaughlin. This method is a true lengthening myoplasty procedure using no intermediate grafts. In general, the results with a 1-stage combination of lengthening temporalis myoplasty and static correction of the lagophthalmos appear comparable with the major series in the literature using free microneurovascular transfers combined with cross-facial nerve grafts for longstanding peripheral monolateral facial paralysis. The obvious advantages of temporalis elongation myoplasty consist in its technical ease, a single step, low incidence of complications and markedly reduced operating time.

[Depressor anguli oris sign (DAO) in facial paresis. How to search it and release the smile (technical note)]. / Signe du Depressor Anguli Oris (DAO) dans les parésies faciales. Comment le rechercher et libérer le sourire (note technique).

INTRODUCTION: After facial paralysis recovery, it is common to note a co-contraction between depressor anguli oris (DAO) muscle and zygomatic muscles. This DAO co-contraction will "obstruct" the patient's smile. The purpose of this technical note is to show how to find the DAO sign and how to free up the smile. TECHNICAL: This co-contraction between the zygomatic muscles and DAO research is placing a finger on marionette line, asking the patient to smile: we perceive a rope under the skin corresponding to the abnormal contraction and powerful DAO. A diagnostic test with lidocaine injection into the DAO can be performed to confirm the diagnosis. The treatment of pathological DAO's contraction can be by injection of botulinum toxin in the DAO, or by surgical myectomy. In all cases, a speech therapy complete the treatment. CONCLUSION: The DAO sign is a semiological entity easy to find. His treatment releases smile without negative effect on the facial expression as the DAO is especially useful in the expression of disgust.

[Sinus pericranii: a rare transcranial venous anomaly]. / Le sinus pericranii: une anomalie veineuse transcrânienne.

INTRODUCTION: Sinus pericranii is a rare midline cranial venous anomaly. It should be diagnosed radiologically. We report an asymptomatic case in a six-year-old female patient. CASE REPORT: The patient consulted for a congenital asymptomatic bluish mediofrontal swelling. The complaint was strictly esthetic. A color US and MR angiography allowed diagnosing a sinus pericranii. Simple surveillance was decided because of a limited esthetic prejudice and the absence of any functional disorder. DISCUSSION: Sinus pericranii is a communication between extra- and intracranial venous systems. Its diagnosis is suspected when a subcutaneous mass is located on the scalp close to the midline, the volume of which changes with the head's position. It is confirmed by MRI, which usually shows a drainage in the superior sagittal sinus. Surgical treatment is a complex procedure and rarely indicated. A simple follow-up is often proposed because of the usual absence of complications.

[Hepatic haemorrhage in pregnancy: a case report]. / Emorragia epatica in gravidanza: caso clinico.

Spontaneous hepatic haemorrhage in pregnancy (SHHP) is a rare event (1 woman out of 15,000). It is generally considered as an advanced state of the microangiopathic hemolytic anemia (HELLP, Hemolysis, Elevated Liver enzyme levels, Low Platelet count). Furthermore, the HELLP is considered as a different form of preeclampsia. The patient, a 33-year-old-woman at 30 weeks' gestation, was admitted to hospital for preeclampsia, underwent an emergency Stark caesarean section with the extraction of an alive foetus and evidence of massive intraperitonal haemorrhage from a large hepatic haematoma. A haemostasis with gauzes of Surgicel was performed, with consequent arrest of the haemorrhage. After approximately 6 hours, a recurrence of the intraperitonal haemorrhage led to a new surgical intervention with hepatic packing with gauzes. After 4 days the patient died. The etiopathogenesis of disease is uncertain, both foetal and maternal mortality are high, and the slight number of reported cases (27) of SPPH from HELLP in international literature offer elements for debate. The following points have been put forward: 1. the monitoring of the counts of the platelets represent the only valid predictive test of HELLP. These concerned women in the third trimester of pregnancy, especially those with a history of preeclampsia; 2. the treatment must be immediate, intensive and multidisciplinary, the plasmapheresis has remarkably improved the prognosis; 3. surgical treatment performed in order to control the SPPH makes use of packing, embolization and/or fastening of the common hepatic artery and, in extreme cases, total hepatectomy with transplantation. The Authors believe it is useful to suggest a national epidemiological research in order to estimate the real incidence of the syndrome in Italy and to establish the guidelines for the medico-surgical treatment.

Coordinated down-regulation of KCNQ1 and KCNE1 expression contributes to reduction of I(Ks) in canine hypertrophied hearts.

OBJECTIVE: In animal models of hypertrophy, electrical remodeling giving rise to QT prolongation occurs rapidly and is associated with the development of torsade de pointes (TdP) arrhythmias and sudden death. Chronic AV block (CAVB)-induced hypertrophy in dogs has been associated with a reduction in the slow component (I(Ks)) of the delayed rectifier potassium current (I(K)), which contributes to a prolongation of ventricular repolarization, the development of an acquired form of long QT, and the substrate for triggered activity and TdP. The present study was designed to probe the molecular basis for the decrease in I(Ks) by studying the characteristics of KCNE1 and KCNQ1, the putative genes responsible for formation of the channel. METHODS AND RESULTS: Using a combination of Northern blot, competitive multiplex PCR and immunoblot assays, we found that CAVB reduces KCNE1 and KCNQ1 RNA in the canine ventricles by 70 and 80%, respectively. Protein levels of KCNE1 and KCNQ1 were reduced by 60 and 50%, respectively. We also demonstrate at the molecular level the basis for inter-ventricular difference in I(Ks) density previously reported in hearts of normal dogs and show the basis for reduction of this difference in the CAVB dog. CONCLUSIONS: Our results indicate that the CAVB-induced reduction in I(Ks) is due to a down-regulation of KCNE1 and KCNQ1 transcription. The data suggest that electrical remodeling of the cardiac ventricle during hypertrophy involves regulation of the gene expression through modulation of transcriptional and translational regulatory pathways. The reduction in KCNE1 and KCNQ1 expression increases the dependence of ventricular repolarization on the rapid component of I(K) and may potentiate the action of Class III antiarrhythmic agents.

Influence of anti-inflammatory agents on the survival of Drosophila.

Various anti-inflammatory compounds were tested for their influence on the life span of the fruit fly (Drosophila melanogaster). 2,3-dihydroxybenzoic acid increased the median life span by 10.9% when fed to adults at a concentration of 1 X 10(-5)M for the entire adult life span. All other anti-inflammatory compounds including acetylsalicylic acid, acetylsalicylic acid plus cupric chloride, Bufferin, chlorpromazine HC1, dimethylsulfoxide, indomethacin, phenol, salicylic acid, and sodium salicylate either decreased or did not change the life span. Rearing flies on 0.5% (0.060M) dimethylsulfoxide caused a 33.3% reduction in life span compared with an 11.8% reduction when fed during adulthood only. At low doses all of the anti-inflammatory compounds including dimethylsulfoxide proved to be nontoxic as measured by changes in life span.

Changes with age in copper and superoxide dismutase levels in brains of C57BL/6J mice.

Superoxide dismutase activity in brains of male C57BL/6J mice decreased with age by 36% on a protein base and by 32% on a DNA base between 50 and 900 days of age. Brain copper increased by 45% up to 600 days of age and appeared to increase slightly from 600 to 900 days of age. Feeding of copper gluconate (5 x 10(-3)M) failed to change the level of copper in either young or old brain, and superoxide dismutase activity was not significantly increased or inhibited by copper feeding. Cupric chloride (2.35 x 10(-6)M) was found to inhibit purified superoxide dismutase (2 x 10(-8)M) by 50%. These observations indicate that brain copper concentrations do not directly determine the activity levels of the copper containing enzyme, superoxide dismutase, under normal ageing conditions.

A new serum alpha-amylase assay of high sensitivity.

The use of chemically modified starch substrates for measurement of serum alpha-amylase activity is described. Action of alpha-amylase on such substrates, in the presence of excess fungal glucoamylase, results in the production of glucose in direct proportion to the amount of alpha-amylase present. The glucose produced is measured by a specific enzymic assay. Results obtained by using this new assay correlate well with activities determined by a conventional saccharogenic assay. The new method is of much higher sensitivity, and is less susceptible to interference, than are most other alpha-amylase assay methods.