[Peripartum cardiomyopathy: incidence, pathogenesis, diagnosis, treatment and prognosis]. / Myocardiopathie du péripartum : incidence, physiopathologie, manifestations cliniques, prise en charge thérapeutique et pronostic.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) is a rare and life-threatening disease of unknown aetiology. The primary objective of this review was to analysed aetiopathogeneses, clinical presentation and diagnosis, as well as pharmacological, perioperative and intensive care management and prognosis of this pathology. METHODS: We undertook a systematic review of the literature using Medline, Google Scholar and PubMed searches. RESULTS: Unlike other parts of the world in which cardiomyopathy are rare, dilated cardiomyopathy is a major cause of heart failure throughout Africa. Its aetiopathogenesis is still poorly understood, but recent evidence supports inflammation, viral infection and autoimmunity as the leading causative hypotheses. This diagnosis should be limited to previously healthy women who present with congestive heart failure (CHF) and decreased left ventricular systolic function in the last month of pregnancy or within 5 months after delivery. Recently, introduction of echocardiography has made diagnosis of PPCM easier and more accurate. Conventional treatment consists of diuretics, vasodilators, and sometimes digoxin and anticoagulants, usually in combination. Patients who fail to recover may require inotropic therapy. In resistant cases, newer therapeutic modalities such as immunomodulation, immunoglobulin and immunosuppression may be considered. Prognosis is highly related to reversal of ventricular dysfunction. Compared to historically higher mortality rates, recent reports describe better outcome, probably because of advances in medical care. Based on current information, future pregnancy is usually not recommended in patients who fail to recover normal heart function. CONCLUSION: PPCM is a rare but serious form of cardiac failure affecting women in the last months of pregnancy or early puerperium. Its aetiopathogenesis is still poorly understood. Introduction of echocardiography has made diagnosis of PPCM easier and more accurate. Prognosis is highly related to reversal of ventricular dysfunction.

[Thrombotic microangiopathies. Incidence, pathogenesis, diagnosis, treatment and prognosis]. / Les microangiopathies thrombotiques. Incidence, physiopathologie, tableau clinique, prise en charge thérapeutique et pronostic.

INTRODUCTION: The objective of this work was to review current data about the pathophysiology, clinical features, and treatment of thrombotic microangiopathies. CURRENT KNOWLEDGE: Thrombotic microangiopathies are microvascular occlusive disorders characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. In thrombotic thrombocytopenic purpura, systemic microvascular aggregation of platelets causes ischemia in the brain and other organs. In the hemolytic-uremic syndrome, platelet-fibrin thrombi occlude predominantly the renal circulation. Thrombotic microangiopathy is a rare disorder whose varied clinical manifestations result from the formation of platelet-rich thrombi within the microvasculature and consequent tissue ischemia. The clinical features are acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. This diagnosis is of considerable importance because of the possible fulminant clinical course. Some atypical forms may be unrecognized. Plasma exchange is the current reference treatment of thrombotic thrombocytopenic purpura. However, in the light of recent publications, either infusions of concentrates of purified enzyme or more intensive immunosuppressive therapy would be more specific.

[Prognostic factors of pneumococcal meningitis. Retrospective study of 31 cases]. / Facteurs de pronostic des méningites à pneumocoque. Etude rétrospective de 31 cas.

AIM: Our aim was to study the susceptibility of Streptococcus pneumoniae to antibiotics in patients with pneumococcal meningitis and to search for the prognosis factors in those patients. METHODS: We have studied retrospectively 31 cases of pneumococcal meningitis. Comparaisons were performed with univariate analysis. RESULTS: The mean age was 36.7 +/- 20.5 years (ranged: 9 and 78 years). The sex ratio was 3,4. The susceptibility of Streptococcus pneumoniae to penicillin G was affected in 10 cases (33% of isolated pneumococcus. The MIC to penicillin G was > or =2 in only one case. The hospital mortality was 26% (8/31). With univariate analysis, factors associated with death were: age > or =55 years (Ss p= 0,006, OR: 17.2 IC95%: 2.3-134), albuminorachie > or = 7 g/l (p = 0.002, OR: 22; IC95%: 1.9-2.51), shock (p = 0.031, OR: 6.7; IC95%: 1.05-42) and Glasgow Coma Score (GCS) < or =8 (p = 0.001, OR: 20; IC95%: 2.68-149). CONCLUSION: No susceptibility to penicillin G is not associated with a worse outcome in patients with pneumococcal meningitis. An age > or =55 years, albuminorachie > or =7 g/l shock and Glasgow Coma Score < or =8 at admission were determinant of the prognosis in our study.

[Thrombotic microangiopathies in the intensive care unit]. / Les microangiopathies thrombotiques en réanimation.

OBJECTIVES: To analyze the clinico-biological manifestations, identify the causes and evaluate the outcome of patients with severe thrombotic microangiopathies admitted in a Tunisian intensive care unit. METHODS: Retrospective study over a period of 10 years (1995-2004) in an intensive care unit. RESULTS: Were included in this study 9 cases with a mean age of 29.2+/-9 years (range 15-44 years). Fever was observed in 5 patients, neurological impairment in 5 and digestive manifestations in 6. Haemolytic anaemia, thrombocytopenia and acute renal failure were observed in 100% of the cases. In our study, the aetiologies of thrombotic microangiopathies were: complicated pregnancy in 6 cases, systemic lupus erythematosus in 1 case. In contrast, no aetiology was found in 2 patients. Plasma exchange was performed in 5 patients, while 4 patients received only plasma infusion. After an average stay of 18+/-12.5 days, evolution was marked by the death 3 patients. CONCLUSION: The incidence of severe thrombotic microangiopathies is rare in Tunisian ICU. The clinical manifestations are not specific. Despite the improvement in the outcome by exogenous plasma supply, thrombotic microangiopathies with severe organ dysfunctions leading to hospitalization in the intensive care unit are associated with a high mortality rate.

[Acute fatty liver of pregnancy. About 22 cases]. / Stéatose hépatique aiguë gravidique. A propos de 22 cas.

OBJECTIVE: To report the clinical experience, biochemical findings, complications and maternal outcome in patients with acute fatty liver of pregnancy (AFLP). PATIENTS AND METHODS: Retrospective study over a period of 11 years (1993-2003). The diagnosis of AFLP was confirmed by liver biopsy in 15 women. However, in 7 women a medical committee that took into account clinical symptoms, and laboratory findings assessed the diagnosis. RESULTS: Were included in this study, 22 women with a mean age of 30+/-5.4 years. Only 22.7% of cases were primigravid. The mean gestational age was 36+/-2.76 weeks (range 31-41 weeks). The fetus was a male infant in 75% of cases. Ten women were admitted in the hospital without jaundice. However 15 women had developed an icterus since their hospital admission or during ICU stay. The mean SAPS II on the ICU admission was of 24.86+/-11.2 points. Biological disturbances observed were mainly: liver cytolysis in 91% of cases, a trend to hypoglycaemia in 86%, a hypoprotidemia in 66.7% and CIVD in 32%. During their ICU stay, 19 women (86.4%) developed one or several organ failures associated to the hepatic failure and 18 women required blood transfusion. After an average stay of 7.5 days, evolution was marked by the death of seven patients (31.8%). Factors correlated with a poor prognosis were: the delay of medical consultation, the development of jaundice, the development of encephalopathy, respiratory or a circulatory failure. DISCUSSION AND CONCLUSION: AFLP is a rare but life-threatening complication. Furthermore AFLP shares features with other more common and less perilous illnesses. An early diagnosis and appropriate therapy of this pathology should improve the poor prognosis in our country.

[Traumatic unilateral renal artery thrombosis and protein C deficiency. A case report]. / Thrombose post-traumatique de l'artère rénale et déficit en protéine C. A propos d'un cas.

Post traumatic renal artery thrombosis is rarely described in the literature. This pathology can result from stretch injury to inelastic intima of the renal artery, or by the direct flow to the abdomen causing compression injury to the renal artery against the vertebral column. However, the association of this pathology with hematologic diseases (in particular protein C deficit) was never described. We report an observation of a 28-year-old man with an uneventful history who was admitted to the intensive care unit for traumatic head injury associated with post traumatic renal artery thrombosis requiring nephrectomy. The etiologic investigation of this thrombo-embolic complication reveals a protein C deficit. Our patient was improved under treatment. This original observation confirms that post traumatic renal artery thrombosis can be associated with hematologic diseases (in particular protein C deficit).

[Celiac disease, cerebral venous thrombosis and protein S deficiency, a fortuitous association?]. / Maladie coeliaque, thrombose veineuse cérébrale et déficit en protéine S, une association fortuite?

INTRODUCTION: Celiac disease is a pathology which is rarely associated with thrombosis complications. Cerebral vascular thrombosis has never been described in patients with a celiac disease. OBSERVATION: We report an observation of a 21-year-old girl with a history of celiac disease who was hospitalized in the intensive care unit for convulsive status epilepticus secondary to a cerebral venous thrombosis. The etiologic investigation of this thrombo-embolic complication revealed protein S deficit. Our patient improved under symptomatic treatment. COMMENT: This original observation confirms that celiac disease can be associated with cerebral venous thrombosis.

[Evaluation of the antibiotics consumption in a Tunisian university hospital]. / Evaluation de la consommation des antibiotiques dans un hôpital universitaire tunisien.

PURPOSE: To estimate the consumption of antibiotics in our hospital and to determine the points at which will be targeted the recommendations of good practice of antibiotherapy. PATIENTS AND METHODS: Our study is a one day prevalence study where antibiotic's prescriptions are analyzed by a group of 6 doctors referents in antibiotherapy. RESULTS: During the study day, 443 patients were studied. Means age was 44.2 +/- 23.3 years (range: 1 and 102 years). 101 infections were diagnosed in 48 patients (10.8%). 192 patients (43.3%) received antibiotics. Antibiotherapy was curative in 44% of cases. The most prescribed antibiotics were gentamicin (85.2 DDD/1000 patients), metronidazole (79 DDD/1000 patients), and cefotaxime (73.9 DDD/1000 patients). According to the evaluation group, 30.7% of the antibiotic's prescription was considered unjustified. The antibioprophylaxis represents the category most often unjustified (49%). The molecules in which prescription was frequently considered unjustified are the ciprofloxacin (67%), the amoxicilline-clavulanate (40%) and the cefotaxime (40%). CONCLUSION: Our results suggest that an action of good practice should be targeted at the antibioprophylaxis and should concern especially molecules in which prescription was frequently unjustified.

[Hemolytic-uremic syndrome secondary to scorpion envenomation (apropos of 2 cases)]. / Le syndrome hémolytique et urémique (SHU) secondaire à une envenimation scorpionique (à propos de deux cas).

HUS was recently described following scorpion sting. We report 2 cases of HUS in the intensive care unit of a university hospital. Two children aged respectively 10 months and 1 year were admitted in the ICU after severe scorpion envenomation (with coma and pulmonary oedema) having required dobutamine and mechanical ventilation. Evolution was marked with acute anaemia without bleeding requiring blood transfusion, acute renal failure, low platelets and signs of haemolysis. Our experience and the previously reported case suggest that scorpion sting could be added to the list of causes of the HUS.

Phenotype and sarcoglycan expression in Tunisian LGMD 2C patients sharing the same del521-T mutation.

Limb-girdle muscular dystrophy type 2C is an autosomal recessive muscular disorder caused by mutations in the gene encoding the gamma-sarcoglycan subunit. This gamma-sarcoglycanopathy is prevalent in Tunisia where only one homozygous mutation a 521-T deletion has been identified. The aim of this study was to carry out a comparative clinical and immunocytochemical analysis of Tunisian patients sharing the same gamma-sarcoglycan gene mutation. One hundred and thirty-two patients were classified as severe, moderate or mild according to a calculated severity score. Heterogeneous phenotypes between siblings were encountered in 75% of the families. The severity of the disease was not found to be related to the age of onset. Immunohistochemical studies of muscle biopsy showed a total absence of gamma-sarcoglycan, a normal or slightly reduced alpha and delta-sarcoglycans whereas the expression of beta-sarcoglycan was variable. The residual sarcoglycan expression was not related to the clinical phenotype. In conclusion, the phenotypic variability in sarcoglycanopathies in Tunisia seems to involve a modifying gene controlling the course of the disease.

Linkage of a new locus for autosomal recessive axonal form of Charcot-Marie-Tooth disease to chromosome 8q21.3.

We report the clinical and genetic linkage analysis of a large Tunisian family with thirteen affected patients suffering from Charcot-Marie-Tooth disease with pyramidal involvement. The inheritance is autosomal recessive. The clinical phenotype is consistent in all patients. It is characterized by onset during the first decade, a progressive course and distal atrophy in all four limbs, associated with a mild pyramidal syndrome. Nerve biopsy in two patients showed severe axonal neuropathy. Genetic linkage excluded known loci of different genetic forms of Charcot-Marie-Tooth disease, familial spastic paraplegia and familial amyotrophic lateral sclerosis. A significant lod score was obtained with marker D8S286, confirming linkage to chromosome 8q21.3. The clinical syndrome observed in this family seems to correspond to a new genetic form of autosomal recessive Charcot-Marie-Tooth disease.

The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy.

Disorganization of the neurofilament network is a prominent feature of several neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy and axonal Charcot-Marie-Tooth disease. Giant axonal neuropathy (GAN, MIM 256850), a severe, autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system, is characterized by neurofilament accumulation, leading to segmental distension of the axons. GAN corresponds to a generalized disorganization of the cytoskeletal intermediate filaments (IFs), to which neurofilaments belong, as abnormal aggregation of multiple tissue-specific IFs has been reported: vimentin in endothelial cells, Schwann cells and cultured skin fibroblasts, and glial fibrillary acidic protein (GFAP) in astrocytes. Keratin IFs also seem to be alterated, as most patients present characteristic curly or kinky hairs. We report here identification of the gene GAN, which encodes a novel, ubiquitously expressed protein we have named gigaxonin. We found one frameshift, four nonsense and nine missense mutations in GAN of GAN patients. Gigaxonin is composed of an amino-terminal BTB (for Broad-Complex, Tramtrack and Bric a brac) domain followed by a six kelch repeats, which are predicted to adopt a beta-propeller shape. Distantly related proteins sharing a similar domain organization have various functions associated with the cytoskeleton, predicting that gigaxonin is a novel and distinct cytoskeletal protein that may represent a general pathological target for other neurodegenerative disorders with alterations in the neurofilament network.

A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3.

Autosomal recessive limb-girdle muscular dystrophies represent a genetically heterogeneous group of diseases characterized by a progressive involvement of skeletal muscles. They show a wide spectrum of clinical courses, varying from very mild to severe. Eight loci responsible for autosomal recessive limb-girdle muscular dystrophies have been mapped and six defective genes identified. In this study, we report the clinical data, muscle biopsy findings and results of genetic linkage analysis in a large consanguineous Tunisian family with 13 individuals suffering from autosomal recessive limb-girdle muscular dystrophy. Clinical features include variable age of onset, proximal limb muscle weakness and wasting predominantly affecting the pelvic girdle, and variable course between siblings. CK rate was usually high in younger patients. Muscle biopsy showed dystrophic changes with normal expression of dystrophin and various proteins of the dystrophin-associated protein complex (sarcoglycan sub-units, dystroglycan, and sarcospan). Genetic linkage analysis excluded the known limb-girdle muscular dystrophies loci as well as ten additional candidate genes. A maximum LOD score of 4.36 at θ=0.00 was obtained with marker D19S606, mapping this new form of autosomal recessive limb-girdle muscular dystrophy to chromosome 19q13.3.

Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency.

The authors report a comparative study of peripheral nerve conductions and nerve biopsy and somatosensory evoked potentials between 15 patients with Friedreich's ataxia and 15 patients with Friedreich's ataxia phenotype with selective vitamin E deficiency. The patients in the two groups are of similar age, age of onset, and clinical phenotype. Peripheral motor nerve action potential amplitude, and conduction velocities are within normal ranges in the two groups. In the Friedreich's ataxia group there is an early and severe peripheral sensory axonal neuronopathy, characterised by an important reduction of the amplitude of sensory action potential, and important loss of myelinated fibres with complete disappearance of large myelinated fibres without any regenerative process. In the Friedreich's ataxia phenotype with selective vitamin E deficiency group there is slight-to-moderate axonal sensory neuropathy with normal to moderate decrease of large myelinated fibre density and important regeneration in nerve biopsy. Somatosensory evoked potentials are markedly involved in the two groups asserting a severe involvement of somatosensory pathway in lumbar, thoracic and cervical spinal cord. These findings suggest that the pathological mechanism involved in the two diseases are different: central peripheral axonopathy in Friedreich's ataxia and central distal axonopathy in Friedreich's ataxia phenotype with selective vitamin E deficiency.

LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3.

Four of the currently recognized autosomal recessive limb-girdle muscular dystrophies (LGMD type 2C-F) are caused by mutations in the genes encoding components of the sarcoglycan complex. LGMD 2C, caused by mutations in gamma-sarcoglycan, is prevalent in northern Africa, especially in Tunisia, where this type of muscular dystrophy was originally described. Although the disease initially was assumed to be genetically homogeneous in this region, linkage to the alpha-sarcoglycan locus (LGMD 2D) has also been found. We have now identified the first Tunisian family with beta-sarcoglycanopathy (LGMD 2E), further adding to the genetic heterogeneity of autosomal recessive LGMD in this population. Direct sequencing of the beta-sarcoglycan gene revealed a homozygous mutation (G272-->T, Arg91Leu) in exon 3. This change affects the same arginine residue in the immediate extracellular domain of the protein that was mutated to a proline (G272-->C, Arg91Pro) in a Brazilian family with a severe form of the disease. Immunohistochemical analysis for the sarcoglycan complex demonstrates absence of the known components of the complex in both of these families. We postulate that the immediate extracellular domain of beta-sarcoglycan may be important for the assembly and/or maintenance of this complex, potentially mediated by disulfide-bond formation to another sarcoglycan via the single cysteine residue in that domain.

Atypical ataxia telangiectasia with early childhood lower motor neuron degeneration: a clinicopathological observation in three siblings.

We report three brothers belonging to a consanguineous family and suffering from ataxia telangiectasia with severe early neurogenic amyotrophy. Pathological examination of the brain and spinal cord in one of them showed Purkinje cell loss with empty baskets and numerous axonal spheroids, dorsal column demyelination with astrocytic proliferation and severe anterior horn cell degeneration. We consider these pathological findings to be related to Louis-Bar disease. Anterior horn cell changes may be one of the early pathological features in ataxia telangiectasia.

Friedreich's ataxia with isolated vitamin E deficiency: a neuropathological study of a Tunisian patient.

The neuropathological findings in a Tunisian patient with Friedreich's ataxia with vitamin E deficiency are reported. The main histological changes are: (1) spinal sensory system demyelination with neuronal atrophy, axonal spheroids and corpora amylacea; (2) neuronal lipofuscin accumulation in the third cortical layer of the cerebral cortex, thalamus, lateral geniculate body, twelfth and ambiguus nuclei, spinal horns and posterior root ganglia. Ultrastructurally, the lipopigments were of uniform granularity without lipid droplets.

Homozygosity mapping of giant axonal neuropathy gene to chromosome 16q24.1.

Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder described as a symmetrical distal neuropathy, with peripheral axons dilated by accumulation of 10 nm neurofilaments (NF) and a severe course of the disease. The observation of kinky or curly hairs is not a constant finding. The GAN1 locus was localized by homozygosity mapping to chromosome 16 q24.1 in a 3 (4) cM interval flanked by the markers D16S3073 and D16S505 (D16S511) in three non-related Tunisian families, showing a genetic homogeneity in these families. Two point lod-score calculation between the linked haplotype and the disease locus was 14.2 at theta(max) = 0. The patients share a slow course of the disease. The differences in the course of the disease between Tunisian and non-Tunisian patients suggest a possible genetic heterogeneity, which is why the present linkage has been referred to as GAN1. The biochemical defect in GAN1 should help to understand the mechanisms involved in NF accumulations as in other neurological diseases (ALS, SMA).

Limb-girdle muscular dystrophy 2C: clinical aspects.

The LGMD2C linked to chromosome 13q and related to a 35 KDa dystrophin-associated glycoprotein deficiency, is very similar to Duchenne muscular dystrophy with an autosomal recessive inheritance. It is characterized by a variability of the age of onset, the severity of the evolution and the severity of myopathic changes at the muscle biopsy. This variability was also present in the expression of the alpha-sarcoglycan between the same sibships and between different families.