"More Guts Than Brains?"-The Role of Gut Microbiota in Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension syndrome (IIH) is most common among obese women. Weight loss is an important factor in improving papilledema. Over the last decade, growing evidence has identified gut microbiota as a potential factor in the pathophysiology of obesity. Accordingly, we investigated whether the gut microbiome is modified in IIH patients compared with healthy controls, and provide possible new treatment venues. METHODS: Shotgun metagenomic sequencing of the gut microbiome of 25 cases of IIH patients (according to the modified Dandy criteria) and 20 healthy controls. Participants were further stratified according to their body mass index. The total DNA from each sample was extracted using the PureLink Microbiome DNA Purification Kit A29789 (Invitrogen, Thermo Fisher Scientific, US). Library preparation was performed using the Nextera DNA Flex Library Prep Kit. Samples were sequenced on the Illumina Novaseq 6000 device. A list of bacterial species that significantly differed between the IIH patients and healthy controls was produced in addition to species diversity. In addition, patients' cohort alone was analyzed, (excluding the healthy controls), and the effect of acetazolamide treatment on their gut microbiota was analyzed. RESULTS: IIH patients have a lower diversity of bacterial species compared with healthy individuals. These bacteria, that is, Lactobacillus ruminis (L. ruminis) (p<6.95E-08), Atopobium parvulum (p<3.9E-03), Megamonas hypermegale (p<5.61E-03), Ruminococcus gnavus (p<1.29E-02), MEL.A1 (p<3.04E-02), and Streptococcus sp. I-G2 (p<3.04E-02), were previously characterized with beneficial health effects. Moreover, we found that Lactobacillus brevis, a beneficial bacterium as well, is more abundant in acetazolamide treated patients (p<7.07E-06). CONCLUSIONS: Gut microbiota plays a potential role in IIH etiology and therefore, can provide a promising new treatment approach for this disease.

Prognostic value of JAK2V617F mutation in pseudotumor cerebri associated with cerebral venous sinus thrombosis.

OBJECTIVES: To examine the clinical characteristics and prognosis of cerebral venous sinus thrombosis (CVST) that presented as pseudotumor cerebri (PTC) patients with JAK2V617F mutation. METHODS: Medical records of all consecutive patients that presented with PTC and a JAK2V617F mutation who were treated were retrospectively reviewed. Data regarding demographics and ocular presenting symptoms and signs, neurological signs, hematological factors treatment, and prognosis were collected. RESULTS: The most common presenting symptoms were headache (5 patients, 83.3%) and visual obscurations (5 patients, 83.3%). CVST of the sagittal sinus and sigmoid sinus were the most common site of thrombus. Platelet count and hemoglobin count were higher than normal during follow-up. There was significant change in the disk edema degree as well as decline in retinal nerve fiber layer (RNFL) thickness (P < 0.001, P < 0.001, Matched pairs). There was no significant change in visual acuity (VA) or mean deviation (MD) during follow-up (P = 0.95, 0.64, respectively, Matched pairs). CONCLUSIONS: Pseudotumor cerebri resulting from CSVT in our patients with JAK2V617F mutation was frequent in young patients and needed medical and surgical treatment, without improvement in visual functions and in third caused poor visual outcome. Therefore, we believe that a screening test for JAK2V617F mutation should be considered for patients with CVST without known risk factor presenting with PTC, especially when sagittal sinus or sigmoid sinus involvement or thrombocytosis or high hemoglobin are found upon presentation. This might lead to more aggressive management which may improve the visual prognosis of those young patients.

A tri-modal distribution of age-of-onset in female patients with myasthenia gravis is associated with the gender-related clinical differences.

BACKGROUND: A tri-modal distribution of age-at-onset emerged among females patients with myasthenia gravis (MG) in our database. This finding may be indicative of different gender-based disease mechanisms. METHODS: We retrospectively reviewed the files of 127 MG patients for the clinical, serology and thymus pathology according to their age at disease onset: ≤40 years (early-onset, EOMG), 40-70 years (intermediate-onset, IOMG) and >70 years (late-onset, LOMG). RESULTS: EOMG was more common among females, and IOMG was more common among males. Ocular MG was more common among the male MG patients with an IOMG. Patients with EOMG had lower rates of positive anti-acetylcholine receptor (anti-AChR). IOMG females, but not IOMG males, had lower rates of positive anti-AChR. IOMG and EOMG females had high rates of thymic hyperplasia, while EOMG males had high rates of thymoma. Comorbidity with autoimmune diseases was common among females with IOMG and LOMG. CONCLUSIONS: The prevalence of IOMG was the reason for the trend reversal of MG prevalence between genders. The clinical features of patients with IOMG differed between genders in the rates of positive anti-AChR, follicular hyperplasia of the thymus and comorbidity with autoimmune diseases. This may suggest a different gender-based mechanism of immune intolerance towards AChR and other antigens.

[WHEN IT SNOWS ALL YEAR ROUND - VISUAL SNOW].

INTRODUCTION: Visual snow is a neurological condition manifested as a prolonged visual experience of small flickering dots encompassing the entire visual field with additional visual and sensory-neural symptoms. The pathogenesis of this disturbance is unknown, although much progress has been made in recent years. The disturbance has been better defined and characterized. Additional insight into the pathological processes that play a role in this phenomenon has been gained, and different treatment modalities have been tried, some with better results. The purpose of this review is to increase awareness of this syndrome.

Quantifying response to intracranial pressure normalization in idiopathic intracranial hypertension via dynamic neuroimaging.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without a clear cause. PURPOSE: To investigate dynamic imaging findings in IIH and their relation to mechanisms underlying intracranial pressure normalization. STUDY TYPE: Prospective. POPULATION: Eighteen IIH patients and 30 healthy controls. FIELD STRENGTH/SEQUENCE: T1 -weighted, venography, fluid attenuation inversion recovery, and apparent diffusion coefficients were acquired on 1.5T scanner. ASSESSMENT: The dural sinus was measured before and after lumbar puncture (LP). The degree of sinus occlusion was evaluated, based on 95% confidence intervals of controls. We studied a number of neuroimaging biomarkers associated with IIH (sinus occlusion; optic nerve; distribution of cerebrospinal fluid into the subarachnoid space, sulci and lateral ventricles (LVs); Meckel's caves; arachnoid granulation; pituitary and choroid plexus), before and after LP, using a set of specially developed quantification techniques. STATISTICAL TESTS: Relationships among various biomarkers were investigated (Pearson correlation coefficient) and linked to long-term disease outcomes (logistic regression). The t-test and the Wilcoxon rank test were used to compare between controls and before and after LP data. RESULTS: As a result of LP, the following were found to be in good accordance with the opening pressure: relative compression of cerebrospinal fluid (R = -0.857, P < 0.001) and brain volumes (R = -0.576, P = 0.012), LV expansion (R = 0.772, P < 0.001) and venous volume (R = 0.696, P = 0.001), enlargement of the pituitary (R = 0.640, P = 0.023), and shrinkage of subarachnoid space (R = -0.887, P < 0.001). The only parameter that had an impact on long-term prognosis was cross-sectional size of supplemental drainage veins after LP (sensitivity of 92%, specificity of 20%, and area under the curve of 0.845, P < 0.001). DATA CONCLUSION: We present an approach for quantitative characterization of the intracranial venous system and its implementation as a diagnostic assistance tool. We conclude that formation of supplementary drainage veins might serve as a long-lasting compensatory mechanism. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:913-927.

Familial Occurrence of Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder of unknown etiology. Its occurrence in the general population is 1/100,000, and 20/100,000 among overweight women of childbearing age. Familial occurrence is reportedly uncommon and not well-characterized. OBJECTIVES: To describe a familial association with IIH. METHODS: We conducted a retrospective chart review of all familial cases of IIH examined in the neuro-ophthalmology clinic of our medical center between January 2006 and June 2013. RESULTS: Of a total of 520 patients with IIH, 15 had other family members with IIH (from seven different families). The family relation was a mother and daughter in two families, a brother and sister in four families, and an aunt and two first-degree cousins in the seventh family. Symptoms, course of disease, and risk factors were similar among the relatives of all seven families, except for the age at diagnosis, which was different in one family. All of the adult patients of six families were obese (body mass index 25-35 kg/m2), and all of the members of the other family were morbidly obese. There was no association between other systemic risk factors and IIH. CONCLUSIONS: IIH occurrence within a family is more common than previously believed, and its incidence in families is more common than in the general population. The clinical course appears to be similar in family members. Our findings suggest a genetic predisposition. Further investigation of familial cases may yield useful information on the pathogenesis and genetic nature of this condition.

Reduced Suprathreshold Odor Identification in Patients with Pseudotumor Cerebri: A Non-Randomized Prospective Study.

BACKGROUND: Recent evidence suggests that olfaction is impaired in patients with pseudotumor cerebri (PTC). OBJECTIVES: To measure suprathreshold olfactory function by using the University of Pennsylvania Smell Identification Test (UPSIT), assessing its usefulness for routine clinical use. METHODS: Forty PTC patients underwent USPIT olfactory testing. RESULTS: Twenty-nine out of 40 (73%) PTC patients (36 women, 4 men; mean age 34 years) had reduced suprathreshold smell sensation according to UPSIT scores: 19 (47%) had mild microsmia, 9 (23%) had moderate microsmia, and one (3%) was classified as having severe microsmia. The mean UPSIT score of all patients was 32.4 (95% confidence interval 31.4-33.4). Multivariate regression analysis found that UPSIT scores were not related to disease activity, disease duration, initial intracranial pressure (ICP), or visual function. CONCLUSIONS: Many PTC patients have reduced suprathreshold olfactory dysfunction that can be discovered by UPSIT, a rapidly administered smell test, which is suitable for clinical office use.

Retina and Nerve Fiber Layer Thickness in Eyes with Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%-5% have severe sight-threatening disease due to optic neuropathy Optical coherence tomography (OCT), the non-invasive imaging technology that yields high-resolution cross-sectional images of the retina, provides qualitative and quantitative data on the retina. OBJECTIVES: To apply this technique to quantitatively assess retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects and in patients with TAO to determine their relationship to the severity of the orbital disease. METHODS: All patients in the ophthalmology clinic who were diagnosed with TAO and underwent OCT imaging as part of their ocular examination comprised the study group, and healthy patients who volunteered to undergo OCT examination served as controls. Results of the complete ophthalmologic examination and OCT findings were collected from medical files, including the thickness of the RNFL and the macula. RESULTS: The study comprised 21 patients and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula thinning compared to healthy subjects. Mean RNFL thickness was correlated with the severity of the orbital disease. CONCLUSIONS: The OCT findings suggest that the retina is involved in TAO, probably as early as the subclinical stage. This highlights the ability of OCT to identify retinal changes earlier and far more accurately than is detected today, enabling earlier diagnosis and more timely treatment to prevent severe visual sequelae.

Pediatric Idiopathic Intracranial Hypertension: Age, Gender, and Anthropometric Features at Diagnosis in a Large, Retrospective, Multisite Cohort.

PURPOSE: To examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, international, multisite study. PARTICIPANTS: Pediatric patients (2-18 years of age at diagnosis) with IIH. MAIN OUTCOME MEASURES: Body mass index (BMI), height, and weight Z-scores; sexual maturation. METHODS: Cases of IIH were identified retrospectively based on diagnostic code, pediatric neuro-ophthalmologist databases, or both and updated diagnostic criteria (2013) were applied to confirm definite IIH. Anthropometric measurements were converted into age- and gender-specific height, weight, and BMI Z-scores CDC 2000 growth charts. When available, sexual maturation was noted. RESULTS: Two hundred thirty-three cases of definite IIH were identified across 8 sites. In boys, a moderate association between age and BMI Z-scores was noted (Pearson's correlation coefficient, 0.50; 95% confidence interval [CI], 0.30-0.66; P < 0.001; n = 72), and in girls, a weak association was noted (Pearson's correlation coefficient, 0.34; 95% CI, 0.20-0.47; P < 0.001; n = 161). The average patient was more likely to be overweight at diagnosis at age 6.7 years in girls and 8.7 years in boys, and obese at diagnosis at age 12.5 years in girls and 12.4 years in boys. Compared with age- and gender-matched reference values, early adolescent patients were taller for age (P = 0.002 in girls and P = 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25% of cases (n = 57/233). Prepubertal participants (n = 12) had lower average BMI Z-scores (0.95±1.98) compared with pubertal participants (n = 45; 1.92±0.60), but this result did not reach statistical significance (P = 0.09). CONCLUSIONS: With updated diagnostic criteria and pediatric-specific assessments, the present study identifies 3 subgroups of pediatric IIH: a young group that is not overweight, an early adolescent group that is either overweight or obese, and a late adolescent group that is mostly obese. Data also suggest that the early adolescent group with IIH may be taller than age- and gender-matched reference values. Understanding these features of pediatric IIH may help to illuminate the complex pathogenesis of this condition.

A case report of ophthalmic artery emboli secondary to Calcium Hydroxylapatite filler injection for nose augmentation- long-term outcome.

BACKGROUND: Filler injection for face augmentation is a common cosmetic procedure in the last decades, in our case report we describe long-term outcomes of a devastating complication of ophthalmic artery emboli following Calcium Hydroxylapatite filler injection to the nose bridge. CASE PRESENTATION: A healthy 24-year-old women received a Calcium Hydroxylapatite filler injection to her nose bridge for the correction of nose asymmetry 8 years post rhinoplasty. She developed sudden right eye ocular pain and visual disturbances. Visual acuity was 20/20 in both eyes and visual field in the right eye showed inferior arch with fixation sparing and supero-temporal central scotoma. Examination revealed marked periorbital edema and hematoma, ptosis, ocular movements limitation, an infero-temporal branch retinal artery occlusion and multiple choroidal emboli. Eighteen months post initial presentation ptosis and eye movements returned normal and choroidal emboli absorbed almost completely. However, visual acuity declined to 20/60, visual field showed severe progressive deterioration with a central and supero-nasal field remnant and the optic disc became pallor. CONCLUSION: Cosmetic injection of calcium hydroxylapatite to the nose bridge can result in arterial emboli to the ophthalmic system with optic nerve, retinal and choroidal involvement causing long term severe visual acuity and visual field impairment.

Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world. METHODS: Retrospective database analysis of adult patients with IIH from 4 different neuro-ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD. RESULTS: The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups. CONCLUSIONS: There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder.

The effect of chemotherapy on optic pathway gliomas and their sub-components: A volumetric MR analysis study.

BACKGROUND: Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeutic dilemma to the treating physicians. While chemotherapy is widely used for these tumors, our ability to predict radiological response is still lacking. In this study, we use volumetric imaging to examine in detail the long-term effect of chemotherapy on the tumor as well as its various sub-components. PROCEDURE: The tumors of 15 patients with OPG, treated with chemotherapy, were longitudinally measured using our novel, previously described volumetric method. Patients were treated with up to five lines of chemotherapy. Sufficient follow-up imaging data, and patient's numbers, allowed for analysis of two treatment lines. Volumetric measurements of the tumors were segmented into solid-non-enhancing, solid-enhancing, and cystic components. Outcome analysis was done per specific treatment line and for the overall follow-up period. RESULTS: An average reduction of 9.7% (±23%) in the gross-total-solid volume (GTSV) was noted following treatment with vincristine and carboplatin. The cystic component grew under therapy by an average of 12.6% (±39%). When measured over the course of the whole study period, the cystic component grew by an average of 35% (±100%) and the GTSV increased by 12% (±35%). CONCLUSION: Initial treatment with vincristine and carboplatin seems to have a minimal initial effect, mostly on the solid components. The cystic component in itself seems to be unaffected by chemotherapy, and contributes to the subsequent growth of the total volume. During the overall treatment period, both solid and cystic components grew regardless of combined treatment methods.

Optic pathway gliomas.

Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-oncology. Recent technological advances in imaging, surgery, and chemotherapy may lead to better understanding of the pathophysiology and better clinical results. This chapter reviews these advances and the current treatment paradigms.

Visual deterioration during pregnancy due to skull base tumors compressing the optic apparatus.

Intracranial tumors may rapidly enlarge during pregnancy. When the tumor abuts the optic apparatus, tumor growth may cause visual deterioration. The decisions regarding the management of these tumors should take into consideration visual function, fetal and maternal safety, and the ability for total resection of the tumor. The objective of the study was to describe our experience and to establish principles for management of intracranial tumors compressing the optic apparatus that present during pregnancy or in the early post partum period. A retrospective case-series review was conducted. Women who presented with visual deterioration either during pregnancy or in the early post partum period due to an intracranial tumor were included. Neurosurgical and obstetrical data were collected from the patients' hospital files and outpatient clinic records. Between 2005 and 2011, nine pregnant women with visual deterioration were diagnosed and treated. Of them, four underwent a neurosurgical procedure during pregnancy. Of the five patients who underwent surgery for tumor resection after delivery, three required urgent cesarean section either due to acute visual deterioration or obstetrical reasons. There was no maternal or fetal mortality and a good overall neonatal outcome was achieved. Improvement in visual acuity and visual fields was achieved in all patients. Postoperative complications included two cases of CSF leak, which resolved after treatment. Visual deterioration during pregnancy due to tumors that compress the optic apparatus requires treatment by a multi-disciplinary team. Surgery is well tolerated by mother and fetus during early and midpregnancy; thus, in cases where visual deterioration is detected, delay of surgery is not justified.

Evidence of multidomain mild cognitive impairment in idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH), a disorder of unknown etiology, may occur in all age groups, but is most common in young obese women. Goals of treatment are to preserve vision and alleviate symptoms, including intractable headache, pulsatile tinnitus, and nausea. Cognitive function is not addressed routinely during clinical evaluation of IIH patients. The aim of our study was to test whether there is cognitive impairment in IIH patients and to evaluate the nature and characteristics of cognitive functions. METHODS: Design-Prospective cross-sectional observational study; Setting-Institutional;Study population-Thirty consecutive IIH patients (3 men and 27 women), mean age at time of testing was 34.4 years; Procedures-All participants completed a cognitive test battery; Outcome measures-Impairment of non-verbal memory, executive function, visual spatial processing, attention, motor skills, problem solving, and information processing speed in IIH patients. RESULTS: Mean scores for all domain index scores were below average for age and education. The global cognitive score, attention, and visual spatial indices had the lowest scores. CONCLUSIONS: Our results indicate that patients with IIH have mild cognitive impairment. All domain measures apart from memory showed a statistically significant difference from normal individuals, indicating that there is a form of multidomain cognitive impairment in IIH. The relationship between cognitive impairment and chronically elevated intracranial pressures and its role in contributing to patient morbidity requires further study.

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.

BACKGROUND: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management. OBJECTIVES: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients. METHODS: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness. RESULTS: Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions. CONCLUSIONS: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

Uncorrected amteropia among children hospitalized for headache evaluation: a clinical descriptive study.

BACKGROUND: Headache is a common complaint in children occasionally requiring hospital admission. The purposes of the present study were to analyze the prevalence of uncorrected ametropia in children with headache admitted to the hospital, and evaluate the importance of refraction assessment as part of their evaluation. METHODS: A retrospective review of children admitted to the Tel Aviv Medical Center for headache evaluation from December 2008 to March 2013, in whom the only abnormality found was an uncorrected refractive error. RESULTS: During the study period 917 children with headache were hospitalized for evaluation and 16 (1.7%) of them (9 boys, mean age 12 years, range 8-18 years) were found to have an uncorrected ametropia. Average headache duration was 4 months (range, 1 week to 1 year) and mean follow-up was 15 months (range, 1 month to 3 years). Twelve (75%) children had brain imaging and 4 children (25%) had a lumbar puncture before their refractive abnormality was identified. Anisometropia and myopia were the most common refractive errors encountered (n = 10 each), followed by hyperopia (n = 6) and astigmatism (n = 3). Despite having uncorrected refractive errors most children (n = 10) did not complain of any visual difficulty. All children were given proper refractive correction and 14 of them reported complete headache resolution on re-examination one month later. CONCLUSIONS: Uncorrected ametropia is a possible cause of headache among hospitalized children. Therefore, complete ophthalmic evaluation, which includes proper refraction assessment, is important as it can identify a treatable headache etiology. Children without visual difficulty should be equally evaluated, as many children with headache and uncorrected amteropia do not have vision complaints.

A genetic survey of patients with familial idiopathic intracranial hypertension residing in a Middle Eastern village: genetic association study.

BACKGROUND: The aim of this study was to determine whether genetic variants are associated with idiopathic intracranial hypertension (IIH) in a unique village where many of the IIH patients have familial ties, a homogenous population and a high prevalence of consanguinity. Several autosomal recessive disorders are common in this village and its population is considered at a high risk for genetic disorders. METHODS: The samples were genotyped by the Ilumina OmniExpress-24 Kit, and analyzed by the Eagle V2.4 and DASH software package to cluster haplotypes shared between our cohort. Subsequently, we searched for specific haplotypes that were significantly associated with the patient groups. RESULTS: Fourteen patients and 30 controls were included. Samples from 22 female participants (11 patients and 11 controls) were evaluated for haplotype clustering and genome-wide association studies (GWAS). A total of 710,000 single nucleotide polymorphisms (SNPs) were evaluated. Candidate areas positively associated with IIH included genes located on chromosomes 16, 8 (including the CA5A and BANP genes, p < 0.01), and negatively associated with genes located on chromosomes 1 and 6 (including PBX1, LMX1A, ESR1 genes, p < 0.01). CONCLUSIONS: We discovered new loci possibly associated with IIH by employing a GWAS technique to estimate the associations with haplotypes instead of specific SNPs. This method can in all probability be used in cases where there is a limited amount of samples but strong familial connections. Several loci were identified that might be strong candidates for follow-up studies in other well-phenotypes cohorts.

The obesity pattern of idiopathic intracranial hypertension in men.

BACKGROUND: Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a disorder of unknown etiology, predominantly affecting obese women of childbearing age. IIH is uncommon in men, with a reported female-to-male ratio of 8:1. The pathogenesis of IIH is poorly understood. Several mechanisms have been suggested, but no one mechanism has been able to account for all manifestations of the disease. This research aims to characterize the obesity phenotype(s) of men with IIH in order to find potential inducers for this disease. METHODS: This is a cross-sectional study based on subjects' medical records. It compared anthropometric parameters between 22 men with IIH, 60 healthy men, and 44 females with IIH. One-way analysis with age and body mass index included as covariates was applied for the assessment of the difference in fat distribution among the three groups. RESULTS: No significant differences were observed between the male IIH cohort and healthy males for age, BMI, and waist measurements, whereas hip circumference was significantly larger in the IIH cohort (114 ± 13 vs. 104 ± 16 cm; respectively, p < 0.001). Consequently, waist-to-hip ratio (WHR) was significantly lower in the male IIH cohort (0.88 ± 0.08 vs. 0.95 ± 0.12; p < 0.001). While no significant differences were observed for age and hip measurements between male IIH and female IIH cohorts, waist circumference and waist-to-hip ratio (WHR) were significantly larger in the male cohort (102 ± 19 cm vs. 95 ± 13 cm, p < 0.001; 0.88 ± 0.08 vs. 0.78 ± 0.06, p < 0.001, respectively). All these results maintained after adjustment for age and BMI. CONCLUSIONS: This is the first report of body fat distribution patterns in men with IIH. Whereas male IIH have larger central fat deposition than female IIH patients, abdominal fatness is less accentuated in IIH men compared to normal obese men. The later observation is in agreement with similar results regarding female IIH patients. We believe that these findings justify further investigation into the involvement of various fat depots in the pathogenesis of IIH in men and women alike.