Congenital malformations at a referral hospital in Gorgan, Islamic Republic of Iran

This study recorded the rate of congenital malformations in 10 000 births at a referral hospital in Gorgan, Islamic Republic of Iran in 1998-99. The overall incidence of congenital malformations was 1.01% (1.19% in males and 0.76% in females). Anomalies of the musculoskeletal system had the highest incidence (0.38%), followed by central nervous system (0.28%) and genitourinary system (0.25%). The incidence of congenital malformations in different ethnic groups was 0.85%, 1.45% and 1.70% in native Fars, Turkman and Sistani groups respectively. Sex and ethnic background are factors in the rate of congenital malformations in this area

High-Flow Vascular Malformations in Children.

Children can have a variety of intracranial vascular anomalies ranging from small and incidental with no clinical consequences to complex lesions that can cause substantial neurologic deficits, heart failure, or profoundly affect development. In contrast to high-flow lesions with direct arterial-to-venous shunts, low-flow lesions such as cavernous malformations are associated with a lower likelihood of substantial hemorrhage, and a more benign course. Management of vascular anomalies in children has to incorporate an understanding of how treatment strategies may affect the normal development of the central nervous system. In this review, we discuss the etiologies, epidemiology, natural history, and genetic risk factors of three high-flow vascular malformations seen in children: brain arteriovenous malformations, intracranial dural arteriovenous fistulas, and vein of Galen malformations

Teratogenic effects of gabapentin on the skeletal system of Balb/C mice fetuses

Objectives: To evaluate the effects of gabapentin )GBP( administration on mice fetuses. Methods: This study was carried out in Birjand University of Medical Sciences during 2008. Thirty Balb/c pregnant mice were divided randomly into 3 groups: 2 experimental groups that received 25 mg/kg )I( and 50 mg/kg )II( of GBP intraperitoneally for the first 15 days of pregnancy, and a control group that received normal saline. External observations of day 18 fetuses and skeleton double staining were performed. Results: Both experimental groups showed similar disorders that can be categorized as the following: 1( decrease of fetal body weight and increase of fetal resorption, 2( macroscopic malformations, and 3( skeletal malformations. Fetal body weights were significantly lower, and fetus resorptions were significantly higher in both treated groups compared to the control group. Macroscopic malformations included exencephaly, limbs defects, brachygnathia, vertebral column deformity, and fetuses with severe retarded growth. Skeletal malformations included delayed ossification, scoliosis, calvaria deformity, and mandibular hypoplasia. Conclusion: This study revealed that GBP can induce previously unreported severe malformations if it is used continuously during the implantation, neurulation, and organogenesis stages of pregnancy. Therefore, it is suggested that great caution should be exercised in using GBP during the early stages of pregnancy until further studies are performed to better understand these effects

A developmental and genetic classification for malformations of cortical development: update 2012.

Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development

Possible role of TORCH agents in congenital malformations in Gorgan, northern Islamic Republic of Iran

This descriptive, cross-sectional study was carried out to explore the frequency of contamination with TORCH agents in neonates with congenital malformations in a referral centre in Gorgan city, Islamic Republic of Iran. Blood samples were taken from 64 neonates and their mothers over a 20-month period in 2003-04. Serologic tests showed that 4/64 infants born with congenital malformations (6%) had positive IgM antibody titres for Toxoplasma gondii (2 cases), rubella virus (1 case) and cytomegalovirus (1 case). IgM was positive in 9/63 mothers (14%), also for T. gondii (3 cases), rubella virus (3 cases) and cytomegalovirus (3 cases). No cases of herpes simplex virus type II or Treponema pallidum were found

Cerebral arteriovenous malformations : usability of Spetzler-Martin and Spetzler-Ponce scales in qualification to endovascular embolisation and neurosurgical procedure

Purpose: Arteriovenous malformations (AVMs) are connected with cerebral haemorrhage, seizures, increased intracranial pressure, headaches, mass effect, and ischaemia symptoms. Selection of the best treatment method or even deciding if intervention is required can be difficult. Material and methods: The study included 50 patients who were diagnosed with cerebral AVMs and treated in our Centre between 2008 and 2014. A total of 111 procedures were performed, including 94 endovascular embolisations and 17 neurosurgical procedures. Medical records and imaging data were reviewed for all patients. All AVMs were measured and assessed, allowing classification in Spetzler-Martin and Spetzler-Ponce scales. Results: Complete or partial treatment was observed in 88.24% of neurosurgical procedures and in 84.00% of embolisations. Early complication rate was 21.28% for embolisation and 17.65% for neurosurgical procedures, while Glasgow Outcome Scale was 4.89 (σ = 0.38) and 5.0 (σ = 0.00), respectively. According to the Spetzler-Martin scale, cerebral haemorrhages occurred more frequently in grade 1, but no statistical significance was observed. In Spetzler- Ponce class B lower grades in Glasgow Coma Scale (GCS) were noticed (p = 0.02). Lower GCS scores were also correlated with deep location of AVM and with eloquence of adjacent brain. Patients with Spetzler-Martin grade 1 were more frequently qualified for neurosurgical procedures than other patients. Conclusions: Treating AVMs requires coordination of a multidisciplinary team. Both endovascular embolisation and neurosurgical procedure should be considered as a part of multimodal, frequently multistage treatment. Spetzler-Martin and Spetzler-Ponce scales have an influence on haemorrhage frequency and patients’ clinical condition and should be taken into consideration in selecting the treatment method

Familial multiple cavernous malformation syndrome : MR features in this uncommon but silent threat

Cerebral cavernous malformations (CCM) are vascular malformations in the brain and spinal cord. The familial form of cerebral cavernous malformation (FCCM) is uncommon. This autosomal dominant pathology mostly presents with seizures and focal neurological symptoms. Many persons affected by FCCM remain asymptomatic. However, acute hemorrhages may appear over time. MRI demonstrates multiple focal regions of susceptibility induced signal loss, well seen on gradient-echo sequences (GRE) or even better on susceptibility-weighted imaging (SWI). The presence of a single CCM – especially in young persons – without history of FCCM does not exclude this diagnosis. Some clinicians also advise an MRI of the spinal cord at the time of diagnosis to serve as a baseline and a control MRI of the brain every one to two years. MRI is certainly indicated in individuals with obvious new neurologic symptoms. Symptomatic siblings should also undergo an MRI of the brain to determine presence, size, and location of the lesions. Even in asymptomatic siblings, a screening MRI may be considered, as there may be an increased risk of hemorrhage, spontaneous or due to the use of certain medications; the knowledge of the presence and the type of these lesions are important. Surgical removal of a CCM may be justified to prevent a life-threatening hemorrhage. Control MRI may reveal the postoperative outcome

Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.

PurposeThe phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.MethodsWe analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.ResultsWe determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding.ConclusionThese findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196

A Case Report and Overview of Familial Cerebral Cavernous Malformation Pathogenesis in an Adult Patient

OBJECTIVE We present a case of a 39 year-old woman who presented with a solitary cavernous malformation hemorrhage without any other lesions, and subsequently presented several months later with a new hemorrhage from a de novo lesion. We discuss mechanisms of paradominant inheritance and haploinsufficiency to describe phenotype expression of familial cavernous malformations. CASE DESCRIPTION The patient presented with unremitting headaches, who had a known history of a solitary cerebral cavernous malformation (CCM) for which she underwent resection several months prior with no evidence of any other CCM lesions seen on post-operative MRI. She has no history of whole brain radiation, family history of cavernous malformations, or prior head trauma. During this hospital visit, she was found to have develop two new lesions in the left fronto-parietal lobe and cerebellum. She was treated with surgical resection of the left frontoparietal lesion, and recovered fully. It is of interest that a patient approaching her fourth decade of life would start to develop formation of multiple de novo cavernous malformations, especially with an absent family history. Paradominant Inheritance and haploinsufficiency are two proposed models of inheritance that can be related to this patient’s disease progression. CONCLUSION The case illustrates an atypical clinical course of a patient with familia