An association of VDR gene polymorphism in hypovitaminosis D mediated secondary hyperparathyroidism in adolescent girls; a tertiary hospital study in central India.

Vitamin D is required to maintain normal serum calcium and phosphate levels that help normal bone mineralization, nerve conduction, muscle contraction, immune function, cell proliferation, and differentiation. Interventions including vitamin D supplementation may not improve vitamin D deficiency, as various complex genomic actions could contribute to vitamin D deficiency in the Indian population. Thus, we assessed hypovitaminosis D's relationship with vitamin D receptor (VDR) gene polymorphism and evaluated parathyroid hormone (PTH) levels in seemingly healthy adolescent school-going girls. We included 100 school-going girls (aged 12-17 years) studying in four schools of different socio-economic strata of Bhopal, India. The selected participants were divided into four groups based on the school in which they were studying. Blood samples were tested for serum calcium, phosphorus, PTH, ALP, vitamin D 25(OH) D, and albumin levels.VDR polymorphism was detected through the PCR-RFLP. Data were analyzed using the chi-square test, ANOVA, and linear regression. The difference in the age, calcium, ALP, and vitamin D values between the four groups were significant (P < 0.05), whereas high PTH levels (80%) were found. A higher prevalence of homozygous polymorphic allele demonstrates a molecular signature for severe secondary hyperparathyroidism. Hypovitaminosis D ranged from 84.9% to 100%, and a high prevalence of VDR polymorphism was observed. Attention must be paid to the health of this age group of school-going girls as hypovitaminosis D and associated VDR gene polymorphism could be the reason for secondary hyperparathyroidism (SHPT), showing changes in bone mineral density in these adolescent girls to ensure their future health.

Pretreatment Normal WM Magnetization Transfer Ratio Predicts Risk of Radiation Necrosis in Patients with Medulloblastoma.

BACKGROUND AND PURPOSE: Radiation necrosis, for which abnormal WM enhancement is a hallmark, is an uncommon complication of craniospinal irradiation in children with medulloblastoma. The magnetization transfer ratio measures macromolecular content, dominated by myelin in the WM. We investigated whether the pretreatment supratentorial (nonsurgical) WM magnetization transfer ratio could predict patients at risk for radiation necrosis after radiation therapy for medulloblastoma. MATERIALS AND METHODS: Ninety-five eligible patients with medulloblastoma (41% female; mean age, 11.0 [SD, 5.4] years) had baseline balanced steady-state free precession MR imaging before proton or photon radiation therapy. Associations among baseline supratentorial magnetization transfer ratio, radiation necrosis (spontaneously resolving/improving parenchymal enhancement within the radiation field)3, age, and the presence of visible brain metastases were explored by logistic regression and parametric/nonparametric techniques as appropriate. RESULTS: Twenty-three of 95 (24.2%) children (44% female; mean age, 10.7 [SD, 6.7] years) developed radiation necrosis after radiation therapy (19 infratentorial, 1 supratentorial, 3 both). The mean pretreatment supratentorial WM magnetization transfer ratio was significantly lower in these children (43.18 versus 43.50, P = .03). There was no association between the supratentorial WM magnetization transfer ratio and age, sex, risk/treatment stratum, or the presence of visible brain metastases. CONCLUSIONS: A lower baseline supratentorial WM magnetization transfer ratio may indicate underlying structural WM susceptibility to radiation necrosis and may identify children at risk for developing radiation necrosis after craniospinal irradiation for medulloblastoma.

Concentration-dependent effect of fumonisin B1 on apoptosis in oesophageal cancer cells.

The geographical distribution of oesophageal cancer is linked to the exposure of fumonisin B1 (FB1), a mycotoxin produced by fungi that contaminates staple food worldwide. Non-genotoxic carcinogens like FB1 disturb homeostasis through increased cell proliferation or suppression of apoptosis. This study investigated the involvement of FB1 (0-20 µM) in spindle-shaped N-cadherin (+) CD45 (-) osteoblastic (SNO) cell death. Cell viability and death were assessed using the MTS and Annexin V-Fluos assays, respectively. Caspase activities were determined luminometrically and the comet assay assessed DNA damage. Induction of oxoguanine glycosylase 1 (OGG1) was measured using quantitative Polymerase Chain Reaction (qPCR), while cleaved poly (ADP-ribose) polymerase 1 (PARP-1) and Bax were determined by western blotting. Cell viability and PARP-1 cleavage were not affected by 1.25 µM FB1, but phosphatidylserine externalization, Bax protein expression, caspase activity, comet tail length and OGG1 transcripts were increased. The reduced cell viability in 10 µM FB1-treated cells was accompanied by corresponding increases in externalized phosphatidylserine, Bax, caspase-3/7 activity and cleaved PARP-1. The OGG1 transcripts were not significantly increased, but comet tails were increased. Bax, caspase-3/7 activities and cleaved PARP-1 were inhibited at 20 µM FB1. In addition, the OGG1 transcript levels were decreased ( p < 0.0001) along with comet lengths ( p < 0.0001). This study showed that FB1-induced apoptosis in SNO cells may be caspase-dependent or caspase-independent; the pathway used depends on the exposure concentration.

Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer.

BACKGROUND: Little information is available about the diagnosis and management of acute methotrexate (MTX)-induced encephalopathy. METHODS: We reviewed clinical and magnetic resonance imaging (MRI) [including diffusion-weighted imaging (DWI)] characteristics of this complication in pediatric cancer patients treated from 2000 to 2006. RESULTS: Six of 754 (0.8%) patients with leukemia or lymphoma and 2 of 44 (4.5%) with bone sarcoma experienced acute encephalopathy within 2 weeks (median, 7.5 days) after receiving high-dose i.v. and/or intrathecal MTX. The signs and symptoms varied at presentation and during episodes: hemiparesis (eight patients, alternating from side to side in four), dysphasia (six), confusion/emotionality (six), headache (three), choreoathetosis (two), and seizure (two). All patients recovered after 1-7 days (median, 5.5 days). DWI revealed restricted diffusion in anatomic brain regions associated with the symptoms; changes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging were consistently less marked. After recovery, DWI findings were normal but T2 and/or FLAIR imaging usually showed residual abnormalities. CONCLUSIONS: Acute MTX toxicity often manifests as fluctuating neurologic symptoms with alternating hemispheric involvement. Restricted diffusion on DWI is a reliable early sign of acute MTX encephalopathy and resolves as clinical status improves, despite the persistence of subtle abnormalities on MRI.

Follow up of patients with colorectal polyps: are the BSG guidelines being adhered to?

OBJECTIVE: The publication of the BSG guidelines in 2002 provided a framework for the follow up of patients with colorectal polyps. The aim of the present study was to determine whether they had, or were being correctly adhered to in a moderately sized District General Hospital. METHOD: A total of 598 patients were on the waiting list for colonoscopy at Airedale General Hospital (AGH) in February 2005. Of these, 203 were being followed up as a result of the previous finding of a polyp. RESULTS: Only 14.8% of patients had been or were being followed up according to the BSG guidelines. The majority of the 85.2% of patients who did not comply with follow up did so as a result of over investigation. Seventy-eight per cent of the low-risk group and 55% of the intermediate-risk group had been colonoscoped, or were waiting to have colonoscopy, too soon or too frequently according to the BSG guidelines. Twenty-four patients with hyperplastic polyps were being followed up incorrectly, as were 17 patients discovered to have a polyp pathology on flexible sigmoidoscopy. It was established that 131 extra colonoscopies had been, or were planned to be performed unnecessarily. CONCLUSION: These data have major implications with regard to patient safety, service provision and cost to the NHS.

Diffusion tensor imaging of tract involvement in children with pontine tumors.

BACKGROUND AND PURPOSE: Conventional MR imaging permits subcategorization of brain stem tumors by location and focality; however, assessment of white matter tract involvement by tumor is limited. Diffusion tensor imaging (DTI) is a promising method for visualizing white matter tract tumor involvement supratentorially. We investigated the ability of DTI to visualize and quantify white matter tract involvement in pontine tumors. METHODS AND MATERIALS: DTI data (echo-planar, 1.5T) were retrospectively analyzed in 7 patients with pontine tumors (6 diffuse, 1 focal), 4 patient controls, and 5 normal volunteers. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated from the diffusion tensor in 6 regions of interest: bilateral corticospinal tracts, transverse pontine fibers, and medial lemnisci. Relationships between FA and ADC values and results of the neurologic examinations were evaluated. RESULTS: The corticospinal tracts and transverse pontine fibers were affected more often than the medial lemnisci. The DTI parameters (FA and ADC) were significantly altered in all tracts of patients with pontine tumors (P < .05), compared with those values in the control groups. A marginally significant (P = .057) association was seen between the severity of cranial nerve deficit and decreased FA. CONCLUSION: DTI provided superior visualization and quantification of tumor involvement in motor, sensory, and transverse pontine tracts, compared with information provided by conventional MR imaging. Thus, DTI may be a sensitive measure of tract invasion. Further prospective studies are warranted to assess the ability of DTI to delineate tumor focality and improve risk stratification in children with pontine tumors.

Diffuse CNS vasculopathy with chronic Epstein-Barr virus infection in X-linked lymphoproliferative disease.

We report a patient with X-linked lymphoproliferative disease (XLP) who developed multiple central nervous system (CNS) manifestations of Epstein-Barr virus infection. XLP, or Duncan syndrome, is a rare inherited disorder characterized by the inability to clear Epstein-Barr virus infection. In addition to Epstein-Barr virus encephalitis, CNS lymphoproliferative disease, and lymphoma, this patient also developed MR angiographic evidence of diffuse fusiform aneurysmal dilation of intracranial vessels.

Encephalopathy in pediatric patients after allogeneic hematopoietic stem cell transplantation is associated with a poor prognosis.

SUMMARY: Encephalopathy is a poorly characterized complication of hematopoietic stem cell transplantation (HSCT). No comprehensive report of encephalopathy exists for children, and the literature contains only a few for adults. We analyzed a large cohort of 405 pediatric patients who underwent allogeneic HSCT during a 10-year period and identified 26 patients (6.4%) who experienced encephalopathy. Identifiable causes of encephalopathy included infection (n=5), single or multiorgan failure (n=4), medication-related complications (n=3), nonconvulsive seizures (n=4), acute disseminated encephalomyelitis (n=2), thrombotic thrombocytopenic purpura (n=2), and stroke (n=1). We were unable to identify the etiology of encephalopathy in five (19%) patients. The prognosis for pediatric patients with encephalopathy was poor: only four (15%) experienced complete neurologic recovery, and 10 (38%) patients experienced partial recovery with residual neurologic deficits. Nine (35%) patients with complete or partial recovery survive long term. A total of 17 patients died; one died of progressive encephalopathy, and 16 died of either relapse of primary disease or toxicity. MRI, CSF analysis including molecular testing for infectious pathogens, and brain biopsy were helpful in obtaining a diagnosis in most of our patients. However, a standardized approach to accurate and timely diagnosis and treatment is needed to improve outcome in these patients.

Morbidity of second-look surgery in pediatric central nervous system tumors.

The extent of brain tumor resection affects survival. Second-look surgery (resection of residual tumor before radiographic progression) may improve survival by reducing the tumor burden, but the morbidity of the procedure is not known. On chart review of 280 patients with two or more brain tumor operations treated between January 1985 and June 1998, we identified 47 patients with second-look surgery. Lansky and Eastern Cooperative Oncology Group (ECOG) performance scores, as well as perioperative complications were recorded. There were 21 gliomas (6 malignant), 12 medulloblastomas, 3 craniopharyngiomas, 3 ependymomas and 8 miscellaneous tumors. Median time to second surgery was 50 days. Perioperative complications occurred in 45% of patients. There was no significant change in the mean Lansky and ECOG scores 4 and 24 weeks after surgery. Gross total resection (GTR) was achieved in 62% of patients and near total resection (NTR) in 23%, and 15% of patients had subtotal resection. GTR or NTR was achieved in 66% of medulloblastomas and 100% of gliomas. We conclude that second-look surgery by experienced pediatric neurosurgeons has an acceptable morbidity and should be considered in patients with residual tumors.

Emergency EEG and factors associated with nonconvulsive status epilepticus.

The purpose of this study was to identify factors associated with nonconvulsive status epileptics (NCSE) and optimize efficient use of emergency electroencephalography (EEG) services. A retrospective review of medical records identified features associated with NCSE over a 1-year period. Seventy-eight EEGs were identified and divided into four groups. Group I, normal EEG; group II, EEG slowing; group III, epileptiform discharges; and group IV, NCSE. Three risk factors were associated with EEG-confirmed NCSE. These three risk factors are: history of epilepsy, witnessed seizure around the time of presentation, and seizure-like motor activity (SLMA). At least one of these three risk factors was identified in 35 patients, and all of the patients with NCSE were within this group. Forty-three patients had absence of these factors, and none of these patients were found to have NCSE, giving these factors a negative predictive value of 100%. Our study suggests that these three factors are highly associated with NCSE. A prospective study should be done to confirm this finding.

HTLV-1 and its neurological complications.

BACKGROUND: Since its discovery in 1980, human T-cell lymphotropic virus type-1 (HTLV-1) has been associated with a number of neurological diseases. The distribution of HTLV-1-associated neurological disease is worldwide. In endemic areas, up to 30% of the population may be infected with HTLV-1; however, only a small percentage of infected persons develops neurological disease. REVIEW SUMMARY: In 1986, HTLV-1 infection was reported in patients of chronic progressive myelopathy of uncertain etiology, and the disease entity was called HTLV-1-associated myelopathy/tropical spastic paraparesis. Recently, HTLV-1 infection has been associated with polymyositis and uveitis. Interestingly, a single patient may display more than one syndrome. Although other neurological syndromes occur in HTLV-1-infected individuals, there is not enough epidemiologic data that show a strong association. Treatment of HTLV-1-associated neurological disease is challenging, and well-controlled studies are lacking. CONCLUSION: As neurologists and other scientists begin to understand the pathophysiology of HTLV-1 infection, improved therapies should be developed. Randomized trials with longer follow-up are required to understand the effect of treatment on disability and quality of life.

Rapid growth of a basilar aneurysm.

We describe a patient who developed, over a 22-month period, a giant aneurysm of his basilar artery. A prior MRI of the brain done for nonspecific symptoms showed a normal brainstem and basilar artery. At presentation, he had a repeat MRI scan for a 4-month history of a partial right oculomotor nerve palsy and left hemiparesis. The MRI revealed a giant aneurysm of the top of the basilar artery. This was treated by angiographic placement of Guglielmi detachable coils (GDC) after surgical intervention was deemed unfeasible. This case illustrates the acquired nature of intracranial aneurysms. All inoperable intracranial aneurysms should be closely monitored and MRI and MR angiography may currently be the best noninvasive methods for this purpose. Intra-arterial GDC embolization of aneurysms is an alternative treatment when surgery is not possible.