Incidence of idiopathic intracranial hypertension in Fife

Background and aims: Idiopathic intracranial hypertension is a clinical syndrome of intracranial hypertension with normal cerebrospinal fluid in the absence of a mass lesion or hydrocephalus on brain imaging. Headache is the most common symptom of idiopathic intracranial hypertension, and about 10-15% of patients suffer from irreversible visual impairment. Previous estimates of the annual incidence of idiopathic intracranial hypertension vary worldwide from 0.03 to 2.2 per 100,000. The major risk factor implicated in idiopathic intracranial hypertension is body mass. Scotland has one of the worst records for obesity in the developed world, and the prevalence of obesity in Fife is higher than the Scottish average. Our aim was to record the incidence of idiopathic intracranial hypertension in NHS Fife over a one-year period. Methods and results: Prospective study including every patient who was seen in the ophthalmology department in NHS Fife with a new diagnosis of idiopathic intracranial hypertension over a one-year period. Thirteen patients were seen with a new diagnosis of idiopathic intracranial hypertension from August 2013 to July 2014 giving an incidence of 3.56 per 100,000. Headache was the most common presenting symptom. Three patients were asymptomatic but were noted to have swollen optic discs during a routine sight test. One patient complained of visual symptoms. All patients were overweight. The mean BMI was 36 (range: 28-49). Conclusion: The incidence of idiopathic intracranial hypertension in NHS Fife was significantly higher than previous estimates in the literature. This is probably due to a high level of obesity in Fife. Scotland is in the midst of an obesity epidemic and if this continues we may see increasing levels of idiopathic intracranial hypertension nationally with associated increasing incidence of visual impairment in young adults.PostprintPeer reviewe

The incidence of idiopathic intracranial hypertension in Scotland : a SOSU study

This study was supported by the Scottish Ophthalmic Surveillance Unit, through the Ross Foundation SOSU study bursary.Background: Idiopathic intracranial hypertension most commonly affects women of childbearing age and usually causes headache and intermittent visual obscurations. Some patients suffer permanent visual loss. The major modifiable risk factor associated with IIH is obesity. Scotland has one of the poorest records for obesity in the western world, with a prevalence in 2016 of 29% in the adult population. We aimed to establish the incidence of idiopathic intracranial hypertension (IIH) in Scotland. Methods: All new cases of IIH seen in Scotland were collected over a 1-year period. Cases were reported by ophthalmologists through the Scottish Ophthalmic Surveillance Unit (SOSU) and by neurologists directly to the investigators using encrypted NHS emails. An open dialogue was maintained between the investigators and specialist neuro-ophthalmology clinics throughout the year to minimise the risk of under-reporting. Cases were defined using the Modified Dandy Diagnostic Criteria. Results: One hundred and forty-four confirmed cases of IIH were reported. One hundred and ten out of 144 patients were female and aged 15–44. The mean BMI in this group was 38.9. Conclusions: The incidence of IIH in Scotland is at least 2.65/100,000. This figure rises to 37.9/100,000 in obese females aged 15–44. This figure is higher than previously published and is probably a result of increasing levels of obesity across the nation. The significant morbidity caused by IIH, in this young population raises the question of whether enough is being done to prevent and treat Scotland’s obesity crisis.PostprintPeer reviewe

Applying a transformative consumer research lens to understanding and alleviating poverty

Increasing attention to global poverty and the development of market-based solutions for poverty alleviation continues to motivate a broad array of academicians and practitioners to better understand the lives of the poor. Yet, the robust perspectives residing within consumer research remain to a large degree under-utilized in these pursuits. This paper articulates how applying a transformative consumer research (TCR) lens to poverty and its alleviation can generate productive insights with potential to positively transform the well-being of poor consumers

Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.

BACKGROUND: Germline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers. METHODS: A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses. RESULTS: Tumour risks analysis provided novel penetrance estimates and genotype-phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%). CONCLUSIONS: Overall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)