Factors predictive of prognosis of infantile spasms. A retrospective study in a low-income country.

PURPOSE: To describe the management of infants with epileptic spasms (ESs) in a low-income country and identify factors predictive of their prognosis. MATERIAL AND METHODS: We conducted a retrospective study in a university hospital in Tunis, Tunisia, over a period of 10 years. We included infants with recurrent ESs. RESULTS: Thirty-eight patients were included. The median age at onset of ESs was 5 months. Typical hypsarrhythmia was found in 21 patients (55%). Brain MRI was done in 32 patients (84%) and metabolic work-up in 34 patients (89%). ESs were categorized as symptomatic in 58% of the patients. Vigabatrin was prescribed as the first-line drug in almost half of the patients. At the last follow-up, 63% of the patients were seizure-free and 82% had a psychomotor delay. The presence of other types of seizures was associated with uncontrolled epilepsy at the last follow-up (P=0.020). The persistence of spasms after the first-line treatment was associated with abnormal final psychomotor development (P=0.047). CONCLUSIONS: Investigation practices and final outcomes of our patients were comparable to data from high-income countries. Treatment practices have been standardized to be in line with international guidelines.

Two cases of sudden death due to pulmonary tumor thrombotic microangiopathy caused by occult gastric carcinoma.

We present two cases of occult gastric carcinoma associated to a large pulmonary tumors thrombosis microangiopathy (PTTM). The first case is a 28 years-old man. He was dead due to a respiratory failure. Autopsy showed a whitish indurated mass invading the stomach wall. Histological findings showed a primary "signet ring" gastric adenocarcinoma with pulmonary carcinomatosis and multiple PTTM and a heart metastasis. The second case is a 24 years-old pregnant woman. The main symptoms were nausea and stomach discomfort and they were seen as pregnancy signs. She was dead because of respiratory failure, 10 hours after a vaginal delivery. Autopsy showed the absence of any cause of death related to the delivery and the presence of a whitish indurated mass in the stomach. Histological findings showed a primary "signet ring" gastric adenocarcinoma, with pulmonary carcinomatosis and multiple PTTM.

Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.

BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.

[Primary cutaneous osteosarcoma]. / Ostéosarcome cutané primitif.

BACKGROUND: Osteosarcoma is a malignant tumor of mesenchymatous origin that chiefly affects the metaphysis of long bones. The extraskeletal form of the disease is rare, and even rarer is a cutaneous site, whether metastatic or primary. Herein, we report a new case of primary cutaneous osteosarcoma. PATIENTS AND METHODS: A 54-year-old woman presented a hard subcutaneous nodular tumor on her left arm noted 1 year earlier. The diagnosis of cutaneous osteosarcoma was made on the basis of histological analysis of the lesion, which showed a sarcomatous dermal-hypodermal proliferation secreting osteoid. Clinical and radiological staging ruled out any extra-cutaneous spread, particularly to bone, thus confirming the primary cutaneous nature of the osteosarcoma. DISCUSSION: Primary cutaneous osteosarcoma is a rare tumor, diagnosis of which is normally based on histopathological features.

A novel 22bp deletion in a Tunisian phenylketonuria family.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase. To date, more than 530 mutations in the PAH gene have been reported. In Tunisia, this disease seems to be the result of point mutations, few studies have been published about molecular defects of PKU in our country. In this study, we report a novel deletion in exon 6 of two brothers in a Tunisian family after DHPLC analysis and sequencing of the exon 6 of the PAH gene.

Controversies in the management of T1 urothelial bladder cancer.

T1 urothelial bladder cancers are in majority high-grade and seem to grow rapidly with the potential not only to recur, but also to progress to muscle invasion. Therefore, management discussions for patients with a high-grade T1 urothelial bladder cancer are critical. In this review, we aim to give an overview of the controversies encountered in the management of these tumors. Relevant information on T1 urothelial cell bladder cancer was identified through a literature search of published studies and review articles. Establishing an accurate diagnosis is of utmost importance in T1 bladder cancer; particularly understaging can adversely impact the survival of the patient. Therefore, a standard re-TUR is highly recommended in all T1 bladder cancer patients. On the other hand overtreatment affects the quality of life and can lead to unnecessary morbidity. The available treatment options range widely: they include transurethral resection alone with or without re-resection, adding intravesical therapy, radical cystectomy, and bladder sparing techniques using radiotherapy or combined chemoradiation. The choice and timing of the decision whether to pursue with conservative management (TUR and BCG) or to proceed with cystectomy (selected cases with adverse prognostic factors) should be continuously reconsidered on an individual patient basis. This is why the decision making is so difficult, and although we have come along a way in understanding the biological behavior of these tumors, both the choice and timing of treatment remain controversial. After ensuring that accurate staging has been done, the therapeutic options for T1 bladder tumors vary widely (from bladder sparing approaches to cystectomy) and a choice should be made based on individual patient basis.

[Rosai-Dorfman disease: therapeutic issues in 2 cases]. / La maladie de Rosai - Dorfman : enjeux thérapeutiques à propos de 2 observations.

Rosai-Dorfman disease (RDD) is a benign lymphoproliferative disorder characterized by cervical lymph node enlargement with a consistent risk of airway compression and esthetic damage. Extranodal localizations are also described. There is no therapeutic consensus for pediatric forms of RDD. Through 2 pediatric cases with nodal involvement in 1 patient and a sinonasal and soft tissue localization in the other, we focus on the management problems of both nodal and extranodal RDD.

Homogénéité mutationnelle de la glycogénose de type Ia en Tunisie.

The glycogen storage disease type Ia (GSD Ia) is a rare inherited disorder, with autosomal recessive determinism. It is characterized by hepatomegaly, short stature and hypoglycemia with lactic acidemia. The confirmation of diagnosis is based on the enzymatic assay performed on liver biopsy. For Tunisians patients, this biochemical test is performed abroad. The aim of our study is the molecular characterization of GSD Ia in Tunisian patients and the development of a molecular diagnosis tool. Our study included 27 patients from 23 unrelated families, mutation analysis revealed that the R83C mutation is the most frequent (65%, 30/46 mutant alleles), followed by the R170Q mutation (30%, 14/46 mutant alleles). The homogeneity of mutation spectrum of GSD Ia in Tunisia allows the development of a cost effective and reliable tool for the confirmation of clinical diagnosis among suspected GSD Ia patients.

Paratesticular Liposarcoma: what is the best Therapeutic Strategy?

Introduction: Liposarcomas are neoplasms of mesodermal origin derived from adipose tissue and correspond to 10-14of all soft tissue sarcomas. Paratesticular liposarcoma is very rare. Case report: We report a 60-year old man who presented with a left testicular tumor 20 cm in diameter. Initial incisional biopsy was reported as fibromatosis. Chest and abdominal CT scan did not show distant metastases. Through an inguinal incision orchidectomy with homolateral inguinal node dissection was performed. Histopathological examination showed a paratesticular myxoid liposarcoma. Adjuvant radiotherapy without chemotherapy was administered. The patient remains well at 11 months followup; with no evidence of recurrence. Conclusion: Complete surgical extirpation reduces the risk of local recurrence. Neoadjuvant chemotherapy or radiotherapy may reduce the tumor size; thus facilitating complete excision

Leukocytoclastic vasculitis and gastric adenocarcinoma.

BACKGROUND: Cutaneous vasculitis has been mainly associated with hematologic cancer. The association of solid neoplasms with cutaneous paraneoplastic vasculitis is rare. We report a case of cutaneous leucocytoclastic vasculitis that revealed a gastric adenocarcinoma. CASE REPORT: A 72-year-old man presented with an acute diffuse polymorphic eruption, with erythematous, vesicular, and necrotic lesions predominating on the lower limbs, which had developed within the past 8 days. The medical history revealed abdominal pain and weight loss over the previous 6 months. A skin biopsy noted typical leucocytoclastic vasculitis. A workup including GI tract investigations revealed an antral adenocarcinoma. Complete excision of the gastric tumor was followed by resolution of the skin lesions. No tumor recurrence or cutaneous vasculitis was noted during 2 years of follow-up. CONCLUSION: To our knowledge, the association of leucocytoclastic vasculitis with gastric cancer has never been reported previously. The failure of vasculitis to respond to conventional therapy should suggest an underlying malignancy.

Phenotypic continuum of type 2 Gaucher's disease: an intermediate phenotype between perinatal-lethal and classic type 2 Gaucher's disease.

The natural history and clinical presentation of the perinatal-lethal Gaucher's disease, a severe variant of acute type 2 Gaucher's disease, is quite different from classic type 2 Gaucher's disease. Rare reported patients had an overlapping phenotype between these two forms confirming that phenotyping may be difficult. Here we report three patients with an intermediate phenotype. The first two patients showed at birth cholestatic jaundice, hepatosplenomegaly and hematological involvement consistent with hemophagocytosis in one patient, the death occurred from a severe liver involvement in one and lung disease in the second in the absence of neurological symptoms. The third patient displayed ichthyosis and facial dysmorphism but with neurological degeneration course and survival consistent with classic type 2 Gaucher's disease.

[Congenital generalized lipodystrophy: a case report with neurological involvement]. / Lipodystrophie congénitale généralisée de type 1 avec atteinte neurologique.

Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by near complete absence of adipose tissue from birth. At least 2 genes located in 9q34 (AGPAT2) and 11q13 (Seipin) are implicated in type 1 and 2, respectively, and result in insulin resistance. We report here a novel case of CGL type 1 resulting from a novel homozygote mutation in the AGPAT2 gene. The clinical picture included pseudoathletic muscular hypertrophy, hypertrophic cardiomyopathy, enlarged liver, hypermetabolism rate, and hyperinsulinemia in a 1-year-old child from Libya. Peripheral hypertonia and reflex excitability revealed signal abnormalities in white matter on magnetic resonance imagery, which has not been described previously in the literature.

[Atypical presentation of Wegener disease in childhood]. / Présentation atypique de la maladie de Wegener de l'enfant.

The pediatric forms of Wegener granulomatosis (WG) are rare. The clinical picture and the profile have specificities compared to those of adults. We report a case of a girl aged of four years and a half who presented initially with a clinical picture of Henoch Schönlein purpura. Physical examination revealed additionally to purpura, scabby lesions on the buttocks. The histopathological examination of a skin biopsy disclosed histiocyte infiltration. There were no Ig A deposits on direct immunofluorescence study. One year later, the diagnosis of WG was suspected, when the patient developed a respiratory problem related to left pulmonary infarction. Screening for thromboembolic factors was positive for antiphosphilipid antibodies. Diagnosis of WG was confirmed by the histopathological study lung tissue and a significant titre of serum ANCA. Blood tests failed to provide evidence of renal involvement. Cyclophosphamide and prednisolone therapy was administrated. A relapse occurred one year later on the controlateral lung; but no biological marker of disease activity could be detected.

Extragastrointestinal stromal tumor of the urinary wall bladder: case report and review of the literature.

Most mesenchymal tumours of the gastrointestinal tract are now referred to as gastrointestinal stromal tumours (GISTs). These tumours typically express c-kit (CD117) and CD34; 30-50% are (often focally) positive for alpha-smooth muscle actin, and all are negative for desmin and S100 protein. Recently, mutations in exon 11 of the c-kit gene have been identified as a molecular genetic marker for the subset of GISTs. In this report, we describe a mesenchymal tumour removed from the pelvic cavity of a 34-year-old man. The tumour was strongly attached to the external wall of the urinary bladder. The neoplasm grossly resembled a leiomyoma, and was histologically composed of sheets of spindle cells with a dense collagenous background. The mitotic activity was low (less then 1 per 50 high-power fields). Immunohistochemically, tumour cells were negative for alpha-smooth muscle actin and desmin and positive for CD117 and CD34. This case illustrates that tumours which are phenotypically and genotypically similar to GISTs may present in sites other than the tubular gastrointestinal tract.

Glycogen storage disease type I in Tunisia: an epidemiological analysis.

OBJECTIVE: Analysis of epidemiological data concerning GSD I in Tunisia. SUBJECTS AND METHODS: All the cases diagnosed as GSD I between 1992 and 2005 in a paediatric department recruiting all the metabolic diseases referred from the North of Tunisia were reviewed. Individual data (sex, socioeconomic and educational background, geographic origins, insurance coverage) were collected and pedigrees were reconstituted. RESULTS: Twenty-two cases (9 boys and 13 girls from 20 homes) were identified. Fourteen belonged to 11 families originating from the North of Tunisia; ten of them are still alive. Both parents in 4 homes (21%) and one parent in 9 homes (47%) were illiterate. Most of the homes (60%) had a low income and 45% comprised at least 3 children. Only 7 homes (35%) had health insurance. Pedigrees indicated 44 infant deaths and at least 10 other cases fulfilling the clinical features of GSD I but not diagnosed. CONCLUSION: The paediatric prevalence of GSD I in the North of Tunisia can be estimated to 7.93 cases per one million inhabitants and its incidence to 1/100,000 births. However, it is likely to be more frequent because of underreporting or underdiagnosis leading to precocious deaths.