Mohsen Javadpour

The Impact of Endoscopic Third Ventriculostomy on the Management of Newly Diagnosed Hydrocephalus in Infants

Objectives: To evaluate the role of endoscopic third ventriculostomy (ETV) as a primary treatment for hydrocephalus in children less than 1 year old and to determine its impact as a whole on the reduction of shunts necessary in a new population of hydrocephalic infants. Methods: Data were collected prospectively on 47 infants with newly diagnosed hydrocephalus of all aetiologies who were referred between 1st April 1998 and 30th September 2000. Twenty-one patients (median age 6 weeks, range 34 weeks of gestation to 10 months) underwent ETV, while the remaining 26 patients had insertion of a ventriculoperitoneal shunt. Anatomical criteria and demonstration of third ventricle outflow obstruction on preoperative magnetic resonance imaging were used to select patients for ETV. Results: There was no mortality or major morbidity following ETV. The median follow-up period was 18 (range 8–36) months. During the follow-up period, the ETV remained patent in 7 (33%) of the 21 patients. Of the 14 patients with failed ETV, 11 had insertion of a ventriculoperitoneal shunt, while 3 have undergone successful redo ETV. Therefore, in total 10 patients (48%) of the ETV group remain shunt independent. The best results were obtained in patients with congenital aqueduct stenosis with 71% (5 of 7 patients) success rate, while patients with posthaemorrhagic hydrocephalus did particularly badly with only 1 of 10 patients having a successful ETV. Overall, 10 of 47 (21%) infants with newly diagnosed hydrocephalus have avoided a shunt. Conclusions: Our results suggest that the selective use of ETV as the primary treatment in infants with hydrocephalus is safe and can lead to a reduction in the shunted population of all newly diagnosed hydrocephalic infants by up to 21%. Success of ETV is aetiology, not age dependent.

Management of cerebral metastasis: Evidence-based approach for surgery, stereotactic radiosurgery and radiotherapy

Brain metastases constitute a significant disease burden and have a major impact on morbidity and mortality. This review discusses the relative merits of open surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), which have been used alone and in combination with varying degrees of success for the treatment of newly diagnosed brain metastasis. Treatment aims to provide disease control with a good quality of life, although prolonged survival may not always be achieved. Decision to treat is based on several prognostic factors including age, performance status and control of the primary cancer. The recently developed disease-specific graded prognostic assessment (DS-GPA) scales can aid in clinical decision making for individual patients. Whole brain radiotherapy remains the mainstay of treatment and provides effective palliation. Omission of WBRT results in worse local and distant control, though not survival. Local tumour control can be achieved by either resection of stereotactic radiosurgery (SRS). In long-term survivors WBRT may cause cognitive decline and SRS is being explored as an alternative method of disease control. Increasingly, quality of life and neuro-cognitive function are being used as end-points in clinical trials.

Sudden death secondary to delayed closure of endoscopic third ventriculostomy

An 11-year-old boy who underwent an initially successful endoscopic third ventriculostomy (ETV) died 4 months later secondary to acute hydrocephalus. This is the first report of sudden death caused by delayed closure of ETV. Guidelines to patients, parents and primary caregivers should include the possibility of ETV failure and encourage early neurosurgical consultation when symptoms of raised intracranial pressure occur.

Presentation, management and outcomes in acute pituitary apoplexy: a large single-centre experience from the United Kingdom

To study the presentation, management and outcomes and to apply retrospectively the Pituitary Apoplexy Score (PAS) (United Kingdom (UK) guidelines for management of apoplexy) to a large, single‐centre series of patients with acute pituitary apoplexy.

The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency

BACKGROUND Adult GHD syndrome is associated with clustering of adverse cardiovascular (CV) risk factors such as abnormal body composition, dyslipidemia, insulin resistance and abnormal haemostatic factors. There is a wealth of evidence linking CV events with elevated levels of inflammatory markers (hs-CRP and IL-6) in the general population; however data on their abnormalities in GHD and specially the effects of GH replacement (GHR) on these inflammatory markers are limited. OBJECTIVE To study the effects of GHR on inflammatory markers, glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease. DESIGN Fifteen hypopituitary adults (11 males, mean age 48.5 years) with recently diagnosed, severe GHD were recruited. Patients received GHR (in addition to other pituitary hormone replacements) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels. Weight, waist hip ratio (WHR), body composition, fasting plasma glucose and insulin, insulin resistance index (HOMA-IR), fasting serum lipid levels, hs-CRP, IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR. RESULTS GHR resulted in a physiological increase in IGF-1 SDS [median -0.6 to +0.39, P<0.0001], improved quality of life (mean pre-treatment AGHDA score 16 vs. post-treatment score 7, P<0.0001) and reduction in WHR (0.94 vs. 0.92, P=0.01). There were no significant changes in body weight and composition. Levels of hs-CRP (log transformed, mean (SD)) were significantly reduced following GHR (pre 1.21 (0.9) vs. post 0.27 (0.9), P<0.0001) but TNF-alpha and IL-6 levels remained unchanged. Fasting glucose (mmol/L) [4.6 (0.1) vs. 5.1 (0.1), P=0.003], fasting insulin (muU/mL) [9.4 (8.1) vs. 12.1 (9.2), P=0.03] and HOMA-IR [1.2 (1.0) vs. 1.5 (1.1) P=0.02] (all pre-GHR vs. post-GHR and mean (SD)) significantly increased following GHR indicating increased insulin resistance. Significant improvements were noted in fasting LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels following GHR [3.4 (0.9) vs. 2.9 (0.7), P=0.03 and 1.2 (0.2) vs. 1.3 (0.2), P=0.02, respectively] (all pre-GHR vs. post-GHR and mean (SD)). Levels of total cholesterol and triglycerides did not change following GHR. CONCLUSIONS Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD resulted in favourable changes in hs-CRP, WHR, fasting LDL-C and HDL-C levels all of which are recognised CV risk markers. However, there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR, monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population.

Pituitary adenomas in childhood, adolescence and young adulthood: presentation, management, endocrine and metabolic outcomes

OBJECTIVE To elucidate the long-term outcomes of pituitary adenomas diagnosed in childhood and adolescence, knowledge of which remains sparse. DESIGN AND METHODS A retrospective review of patients aged ≤21 years at diagnosis of pituitary adenoma, attending a neuroendocrine service in Liverpool, UK, between 1984-2009. RESULTS There were 41 patients (33 female), mean age at diagnosis 17.3 years (range 11-21) and mean follow-up 9.6 years; 29 patients had prolactinomas (15 macroprolactinomas), 6 non-functioning pituitary adenomas (NFPAs), 5 Cushings disease (CD) and 1 acromegaly. All prolactinoma patients received dopamine agonists (DAs) and three also underwent pituitary surgery. Furthermore, ten patients underwent surgery: five with CD, one with acromegaly and four with NFPA. Four received radiotherapy after surgery. Another ten patients received hormone replacement: nine hydrocortisone, five thyroxine, seven sex steroids and five GH; another seven had severe asymptomatic GH deficiency. Three female patients were treated for infertility (two successfully). Thirteen patients gained significant weight (body mass index (BMI) increase >2 kg/m(2)) since diagnosis and 16 in total are now obese (BMI>30 kg/m(2)). Five were treated with orlistat and one attended a weight management service. Two received antihypertensive medications, two had type 2 diabetes and four were treated for dyslipidaemia. CONCLUSIONS This is one of the largest reviews of patients aged 21 or younger at diagnosis of pituitary adenoma followed up by a single service. Two-thirds had prolactinomas, all were treated with DAs and three underwent surgery. Increased cardiovascular risk factors (obesity and dyslipidaemia) and infertility are important sequelae and active identification and treatment are necessary.

Atypical meningoma: current management dilemmas and prospective clinical trials

Atypical meningioma is an intermediate grade tumour with a greater risk of recurrence following surgical resection. Changes to the WHO classification have resulted in an increased reporting of these tumours. The role of early adjuvant radiotherapy after gross total resection has not been clearly defined and the literature evidence is of poor quality providing conflicting information. This review assesses the evidence for current clinical practice, management dilemmas and the need for prospective clinical trials for atypical meningioma.

The d3/fl-GH receptor gene polymorphism does not influence quality of life and body composition in GH-deficient adults receiving GH replacement therapy.

CONTEXT The growth response to recombinant human growth hormone (rhGH) in GH deficient (GHD) patients may be influenced by polymorphisms in the growth hormone receptor (GHR) gene. OBJECTIVES To investigate adults with GHD who have been treated with rhGH for more than 1 year to determine the relationship between genomic deletion of exon 3 in the GHR gene and quality of life (QoL), body composition (BC) and serum IGF1 levels, and to compare these variables to a healthy adult control population. DESIGN Cross-sectional study. METHODS A total of 100 healthy adult controls and 131 patients were studied. Deletion of exon 3 in the GHR gene was determined in DNA that was isolated from peripheral blood. QoL was determined using the adult GHD assessment scale and three other validated QoL instruments. RESULTS In the control population, the frequency of the genotypes was 53% fl/fl, 40% d3/fl and 7% d3/d3, and in the patient population, 55, 39 and 6% respectively. There was no significant difference in QoL scores and BC in control subjects with the fl/fl genotype compared with those with the d3/d3 or fl/d3 genotype. There was no difference in the rhGH dose required to optimize serum IGF1, QoL or BC in patients with the fl/fl genotype compared with those with the d3/d3 or d3/fl genotype. CONCLUSION Deletion of exon 3 in the GHR gene does not influence adult height, QoL or BC of the normal adult population nor does it influence rhGH dose, QoL and BC in GHD adults treated with rhGH for more than 1 year.

Intracerebral abscess formation following embolisation of an internal carotid artery aneurysm using Guglielmi detachable coils.

Summary¶Infection following endovascular therapy for cerebrovascular disease is a potential but rare complication. A 70-year-old lady in whom an intracranial abscess formed secondary to GDC embolisation of a giant right internal carotid artery aneurysm is reported. Computed tomography (CT) showed the abscess and staphylococcus aureus was cultured from the cerebrospinal fluid and blood. The abscess was successfully treated by antibiotic therapy. Infected Guglielmi detachable coils (GDC) may result in abscess formation in the presence of underlying cerebral ischaemia.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage

The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long‐term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients’ acute admission with SAH could predict the occurrence of long‐term hypopituitarism.