Working collaboratively between the Academic Unit of Ophthalmology, School of Immunity and Infection and the Centre for Diabetes, Endocrinology and Metabolism, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Alex Sinclair worked as an MRC Clinical Research Training Fellow (2005 – 2010). She sought to define 1) an evidence base for treatment and 2) the pathogenesis, of idiopathic intracranial hypertension (IIH).
During the fellowship she conducted a study which provided the first evidence that weight loss is effective at reducing not only headaches and papilloedema, but also intracranial pressure (ICP) in IIH (BMJ 2010;341:c2701). In-vitro and ex-vivo studies addressed the role of obesity and 11B hydroxysteroid dehydrogenase (11B HSD1) a regulator of local cortisol availability, in the regulation of ICP and IIH. She demonstrated expression and activity of 11B HSD1 in the choroid plexus, the cerebrospinal secreting tissue and showed that therapeutic weight loss in IIH was associated with a reduction in global 11β-HSD1 activity, and additionally that the reduction in 11β-HSD1 correlated with weight loss. These studies suggest that elevated 11β-HSD1 may represent a pathogenic mechanism in IIH and inhibition of 11β-HSD1 may have therapeutic potential in IIH.
Alex plans to continue work within the field of idiopathic intracranial hypertension and headcahe and is currenly establishing new tranlational studies in this area. In association with Professor Ann Logan’s research group (Neurobiology and Neuropharmacology) she is collaborating on research programs involving intracranial pressure dynamics whilst maintaning links with Professor Paul Stewart’s research group (Centre for Diabetes, Endocrinology and Metabolism, School of Clinical and Experimental Medicine) to expand work on the involvement of steroid hormones and 11B HSD1 in intracaranial presure regualtion.
Sinclair AJ, Kuruvath S, Sen D, Nightingale PG, Burdon MA and Flint G. (2011), Is Cerebrospinal Fluid Shunting in Idiopathic Intracranial Hypertension Worthwhile? A 10 year review. (Cephalalgia Oct 3. [Epub ahead of print])
Ball AK, Howman A, Wheatley K, Burdon MA, Matthews T, Jacks AS, Lawden M, Sivaguru A, Furmston A, Howell S, Sharrack B, Davies MB, Sinclair AJ, Clarke CE. (2011), A randomised controlled trial of treatment for idiopathic intracranial hypertension. J Neurol. May;258(5):874-81. . May;258(5):874-81.
Sinclair AJ, Walker EA, Burdon MA, van Beek AP, Kema IP, Hughes BA, Murray PI, Nightingale PG, Stewart PM, Rauz S and Tomlinson JW. (2010), Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients 1 with Idiopathic Intracranial Hypertension: a link between 11β-HSD1 and intracranial pressure regulation? J Clin Endocrinol Metab; 95(12):5348-56
Sinclair AJ, Burdon MA, Ball AK, Nightingale NG, Good P, Matthews TD, Jacks A, Lawden M, Clarke CE, Walker EA, Tomlinson J, Stewart PM, Rauz S. (2010), Low calorie diet and intracranial pressure in idiopathic intracranial hypertension: a prospective cohort study . BMJ. 7;341:c2701.
Sinclair AJ, Viant MR, Ball AK, Burdon MA, Walker EA. Stewart PM, Rauz S, Young S. (2010), NMR-Based Metabolomic Analysis of Cerebrospinal Fluid and Serum in Neurological Diseases - A Diagnostic Tool? NMR Biomed Feb;23(2):123-32.
Ball A*, Sinclair AJ*, Curnow SJ, Tomlinson JW, Burdon MA, Walker EA, Stewart PM, Nightingale PG, Clarke CE, Rauz S. (2009), Elevated CSF leptin in idiopathic intracranial hypertension: Evidence for hypothalamic leptin resistance? Clin Endocrinol (Oxf).70(6):863-9. *Share the role as first author
Sinclair AJ, Ball AK, Burdon MA, Clarke CE, Stewart PM, Curnow SJ, Rauz S. (2008),Exploring the Pathogenesis of Idiopathic Intracranial Hypertension: An inflammatory perspective. J Neuroimmunol.15;201-202:212-20. Epub 2008 Aug 3
Sinclair AJ, Onyimba C, Khosla P, Hughes S, Tomlinson J, Stewart P, Burdon M, Murray P, Walker E, Rauz S. (2007) Corticosteroids, 11β-Hydroxysteroid Dehydrogenase Isozymes and the Rabbit Choroid Plexus. J Neuroendocrinol;19(8):614-620