An autosomal recessive leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa maps to chromosome 17q24.2-25.3

Background Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. To identify new genes responsible of such diseases, we studied a consanguineous Moroccan family with three affected individuals displaying hereditary leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa that appears to segregate in autosomal recessive pattern. Methods All family members underwent neurological and radiological examinations. A genome wide search was conducted in this family using the ABI PRISM linkage mapping set version 2.5 from Applied Biosystems. Six candidate genes within the region linked to the disease were screened for mutations by direct sequencing. Results Evidence of linkage was obtained on chromosome 17q24.2-25.3. Analysis of recombination events and LOD score calculation suggests linkage of the responsible gene in a genetic interval of 11 Mb located between D17S789 and D17S1806 with a maximal multipoint LOD score of 2.90. Sequencing of seven candidate genes in this locus, ATP5H, FDXR, SLC25A19, MCT8, CYGB, KCNJ16 and GRIN2C, identified three missense mutations in the FDXR gene which were also found in a homozygous state in three healthy controls, suggesting that these variants are not disease-causing mutations in the family. Conclusion A novel locus for leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa has been mapped to chromosome 17q24.2-25.3 in a consanguineous Moroccan family

l\'Actinomycose Cérébrale Cerebral Actinomycosis (Francais)

Actinomycosis is a saprophytic infection. The most frequent sites are the cervico-oro-facial area, the abdomen and lungs. Central nervous system involvement in an actinomycotic infection is uncommon, it does not seem to exceed 2, 8% of cases. Radiological procedures are of great help in locating the lesion and delineating its relationships with the surrounding structures. Diagnosis is based on the laboratory evidence. We report the case of a 45 years old patient, who had seizures eight years after head traumatism. The CT scan and MRI showed an heterogeneous frontal lesion with cystic posterior part and multilocular anterior component, associated to a bone defect. The diagnosis of cerebral actinomycosis was confirmed by the histological study. The patient had a surgical ablation and antibiotherapy. Résumé L\'actinomycose est une maladie infectieuse qui touche les régions cervico-faciale, abdominales et thoraciques. L\'atteinte cérébrale est inhabituelle puisqu\'elle est rencontrée dans moins de 2,8% des cas. L\'imagerie joue un rôle important dans le diagnostic topographique et différentiel et oriente l\'abord chirurgical pour un examen anatomo-pathologique. Nous rapportons l\'observation d\'un patient âgé de 45 ans ayant présenté des crises comitiales grand mal 8 ans après un traumatisme crânien. Le scanner et l\'IRM ont montré un processus lésionnel frontal droit hétérogène avec une composante kystique et multiloculée, en regard d\'un defect osseux. Le diagnostic d\'une actinomycose cérébrale a été confirmé par l\'étude histologique. Le patient a bénéficié d\'une ablation chirurgicale avec une antibiothérapie. (Af. J. of Neurological Sciences: 2003 22(1)

Vertebral Hemangiomas - Aggressive Forms

Les Hemangiomes Vertebraux Agressifs (Francais) Résumé  Introduction Les hémangiomes vertébraux sont des tumeurs bénignes généralement asymptomatiques. Les tumeurs agressives représentent moins de 1% des cas. L\'imagerie permet de poser le diagnostic positif et le degré d\'agressivité. Objectif Evaluer le rôle des examens radiographiques et des moyens thérapeutiques, embolisation, chirurgie, vertébroplastie, radiothérapie en présence d\'un hémangiome vertébral. Méthodes Il s\'agit d\'une étude rétrospective de 5 patients dont l\'âge moyen était de 20 ans. La symptomatologie clinique était celle d\'une compression médullaire d\'installation progressive dans tous les cas. Les radiographies standards, la TDM et l\'IRM sont réalisées chez tous les patients. Résultats Les hémangiomes vertébraux étaient localisés au niveau du rachis cervical C4 dans un cas et dorsal (D3-D9) dans 4 cas. La radiographie standard a montré un aspect classique de vertèbre grillagée. L\'IRM a objectivé un aspect hétérogène des vertèbres atteintes avec des zones vides de signal d\'aspect serpigineux et des zones d\'hyper signal et d\'iso signal en Tl aug - mentant en T2. la composante épidurale responsable de la compression médullaire présente les mêmes caractéristiques de signal que la lésion vertébrale. Devant cet aspect 2 patients ont bénéficié d\'une embolisation préopératoire. Conclusion Le diagnostic des hémaniomes vertébraux agressifs est aisé grâce à l\'imagerie par l\'analyse de l\'architecture lésionnelle et de l\'étendue épidurale. Elles permettent d\'établir un score d\'agressivité qui oriente l\'attitude thérapeutique. La conduite thérapeutique qui nous semble la mieux adaptée devant ces hémangiomes agressifs reste l\'association d\'une embolisation avec une vertébroplastie percutanée associée éventuellement à une chirurgie en cas d\'atteinte épidurale. Background Vertebral hemangiomas are benign tumours and are rarely symptomatic. Aggressive forms represent less than 1% of all cases. Medical imaging allows both diagnosis and evaluation of their aggressivity. Objective To assess the role of radiology, embolisation, percutaneous vertebroplasty, radiotherapy and surgery in the diagnosis and treatment of vertebral hemangiomas. Methods We report our experience of five patients who had an average age of 20 years. They all presented with progressive medullary compression and were investigated with plain xrays, CT and MRI. Results The vertebral hemangiomas were located in the cervical spine at C4 in one patient and between D3 and D9 in the other four. Plain xrays showed the classic vertical striations and MRI revealed a heterogeneous picture with attenuation of signal in some and hyper or iso intense signals on T1 and hyper intense T2 in the others. The epidural component presented the same imaging characteristics as the bony lesions. Two of our patients were embolised before surgery. Conclusion Analysis of the radiological and imaging characteristics of these lesions make vertebral hemangiomas relatively easy to diagnosed. This analysis also enables an aggressivity score to be established that can help guide the therapeutic options. Our treatment strategy included preoperative embolisation vertebroplasty and surgery when the epidural space was invaded. Keywords: Angiome, Hémangiome vertébral, Rachis , Radiologie, Vertébroplastie, Hemangioma vertebral, Radiology, Percutaneous vertebroplasty, Spine angioma Af J Neuro Sci: 2002 21(1

Homozygous mutation in the ADH6 gene, involved in alcohol metabolism, associated with a multisystem disorder, analogous to the fetal alcohol syndrome

Introduction: In humans, there is considerable individual variability in ethanol metabolism, and these differences have been partially attributed to genetic variability at the ADH locus at 4q22-23, where seven genes are found. They encode ADH enzymes with different kinetic and structural properties that represent the first step in a series of reactions involved in the metabolism and elimination of alcohol from the body. The objective of the study was to identify the potential genetic cause in a patient with congenital metabolic encephalopathy of unknown etiology, and having similarities to fetal alcohol syndrome. Case: We described a patient of Moroccan origin who suffered from a multisystem disorder compatible with congenital metabolic encephalopathy. The main clinical characteristics observed in the patient were psychomotor retardation, facial dysmorphism, microcephaly, and hematologic and endocrine abnormalities. Whole exome sequencing identified a homozygous missense mutation c.133G > A (p.Gly45Arg) in ADH6, a gene implicated in alcohol metabolism and previously not associated with human disease. The variant segregates well with the disease in the family, affects a highly conserved amino acid and was predicted to be damaging. Bioinformatics analysis revealed that the Gly45Arg substitution may affect the structure and function of the ADH6 protein. No other potential causal gene under an autosomal recessive inheritance model was found. Discussion: The patient presented with a congenital metabolic encephalopathy, and having similarities to fetal alcohol syndrome due to prenatal alcohol exposure. The only potential causing variant was identified in the ADH6, belonging to the Class V ADH which is a predominantly fetal alcohol dehydrogenase. In addition, he presented vacuolated lymphocytes, anemia and abnormalities of endocrine function, all have been reported to be related to an abnormal alcohol metabolism. Conclusion: We identified a novel variant in ADH6, involved in the metabolism of alcohol, in a patient with a hereditary alcohol metabolism encephalopathy syndrome

Les hemangiomes vertebraux agressifs

Background Vertebral haemangiomas are benign tumors rarely symptomatic. Aggressive formes represents less than 1% of all cases. Medical imaging allows both diagnosis and evaluation of the agressivity . Objective The purpose is to assess the role of radiology, embolisation, percutaneous vertebroplasty , radiotherapy and surgery in diagnosis and treatment of vertebral hemangioma. Methodology This retrospective stydy reports our experience about five patients . In all of them radiographies, CT and an RMI has been performed . Results The average age was 20 years. The symptomatology was made of a progressive medullar compression in all the cases. Vertebral haemangiomas were localised at the cervical spine C4 in one case and at dorsal ( D3-D9) in the 4 other cases. Radiographies showed the classic vertically striated vertebra. MRI revealed heterogenous vertebras with empty signal zones and others of hyper signal or iso signal in T1 increased in T2. Epidural component was presenting the same radiological characterstics as the vertebral lesions. Two of our patients had an embolization before surgery. Conclusion Vertebral haemangiomas diagnosis is easy with radiological criteria by analysing the architecture of the lesion and its epidural spreading . It allows establishing an agressivity score that guides the therapeutic attitude. The treatment attitude we adopt associate embolization, vertebroplasty and surgery when there epidural space is invaded