Anat Kesler

Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease

OBJECTIVESnMild cognitive impairment (MCI) may represent a transition to early Alzheimers disease (AD). The retinal nerve fiber layer (RNFL) is composed of axons originating in retinal ganglion cells that eventually form the optic nerves. Previous studies have shown that degenerative changes occur in optic nerve fibers and manifested as thinning of RNFL in patients with AD. The objective of this study was to assess the relationship between MCI, AD and loss of RNFL.nnnPATIENTS AND METHODSnIn this study, patients fulfilling diagnostic criteria for MCI (n=24), AD (n=30) and cognitively normal age-matched controls (n=24) have undergone neuro-ophthalmologic and optical coherence tomography (OCT) examinations to measure RNFL thickness.nnnRESULTSnThere was a significant decrease in RNFL thickness in both study groups (AD and MCI) compared to the control group, particularly in the inferior quadrants of the optic nerve head, while the superior quadrants were significantly thinner only in AD. Although AD patients may have more severe changes than MCI cases, the differences were statistically nonsignificant. Furthermore among AD patients, there was no relation to the severity of the dementia.nnnCONCLUSIONSnOur data confirm the retinal involvement in AD, as reflected by loss of axons in the optic nerves.

Idiopathic Intracranial Hypertension Is Associated with Lower Body Adiposity

OBJECTIVEnTo characterize the obesity phenotype(s) in patients with idiopathic intracranial hypertension (IIH).nnnDESIGNnDatabase study.nnnPARTICIPANTSnWe studied 44 consecutive patients with IIH, in addition to 184 women attending the obesity clinic of the same medical center and 199 obese women participating in the first Israeli national survey on health and nutrition conducted in 1999 and 2000.nnnMETHODSnAnthropometric parameters were compared with those of 2 control groups of the same age range.nnnMAIN OUTCOME MEASURESnWeight, height, and waist and hip circumference were measured.nnnRESULTSnForty subjects, comprising 91.0% of this cohort, were either overweight (body mass index, 25.0-29.9 kg/m(2)) or obese (body mass index > or = 30 kg/m2). Mean waist circumference was 95.3 cm for IIH, 99.8 cm for the national survey, and 114.5 cm for the obesity clinic cohort (P<0.001), whereas hip circumference was 121 cm for IIH, 118.4 cm for the national survey, and 125.8 cm (P = not significant) for the obesity clinic cohorts. Waist-to-hip ratio, a descriptive measure of body fat distribution approximately reflecting upper to lower body fat ratio, was 0.79 in the patients with IIH, 0.84 in the national survey group, and 0.91 in the obesity clinic cohort (P<0.001; all comparisons were adjusted for age and body mass index).nnnCONCLUSIONSnIn IIH, fat tends to preferentially accumulate in the lower body relative to other obese women of the same range. Whereas most complications of obesity, such as hypertension, diabetes, dyslipidemia, and the metabolic syndrome, are linked to upper body adiposity, IIH may represent a unique condition potentially induced by nonvisceral fat-related mechanisms.nnnFINANCIAL DISCLOSURE(S)nThe authors have no proprietary or commercial interest in any materials discussed in this article.

The efficacy of optic nerve ultrasonography for differentiating papilloedema from pseudopapilloedema in eyes with swollen optic discs

Purpose:u2002 To evaluate the diagnostic yield of optic nerve ultrasonography (US) in distinguishing between papilloedema (swollen discs owing to raised intracranial pressure) and pseudopapilloedema.

Shedding light on walking in the dark: the effects of reduced lighting on the gait of older adults with a higher-level gait disorder and controls

ObjectiveTo study the effects of reduced lighting on the gait of older adults with a high level gait disorder (HLGD) and to compare their response to that of healthy elderly controls.Methods22 patients with a HLGD and 20 age-matched healthy controls were studied under usual lighting conditions (1000 lumens) and in near darkness (5 lumens). Gait speed and gait dynamics were measured under both conditions. Cognitive function, co-morbidities, depressive symptoms, and vision were also evaluated.ResultsUnder usual lighting conditions, patients walked more slowly, with reduced swing times, and increased stride-to-stride variability, compared to controls. When walking under near darkness conditions, both groups slowed their gait. All other measures of gait were not affected by lighting in the controls. In contrast, patients further reduced their swing times and increased their stride-to-stride variability, both stride time variability and swing time variability. The unique response of the patients was not explained by vision, mental status, co-morbidities, or the values of walking under usual lighting conditions.ConclusionWalking with reduced lighting does not affect the gait of healthy elderly subjects, except for a reduction in speed. On the other hand, the gait of older adults with a HLGD becomes more variable and unsteady when they walk in near darkness, despite adapting a slow and cautious gait. Further work is needed to identify the causes of the maladaptive response among patients with a HLGD and the potential connection between this behavior and the increased fall risk observed in these patients.

OCT assessment of morphological changes of the optic nerve head and macula in idiopathic intracranial hypertension

OBJECTIVEnTo assess the morphologic changes of the optic nerve head and macula in patients with idiopathic intracranial hypertension (IIH) with optical coherence tomography (OCT).nnnMETHODSnData was extracted from the medical records and Stratus OCT images of IIH patients.nnnRESULTSnNinety-one eyes of 48 IIH patients were divided into 3 groups according to their clinical optic disc appearance. Average retinal nerve fiber layer (RNFL) thickness was statistically different between the groups: normal optic disc/mild elevation group (N=20) - 89 μm (95% CI, 80-98 μm), mild elevation group (N=51) - 109 μm (95% CI, 101-117 μm), and papilledema group (N=20) 124 μm (95% CI, 100-153 μm) (P=0.004). Fast macular thickness map did not demonstrate a significant difference between the groups for most measured macular areas (N=49 eyes).nnnCONCLUSIONSnPeripapillary RNFL measurements correlated with the clinical appearance of the optic discs, suggesting that OCT may assist in the follow up of IIH patients.

Hyperandrogenism is Associated with Earlier Age of Onset of Idiopathic Intracranial Hypertension in Women

Abstract Purpose: Previous reports have connected between Idiopathic intracranial hypertension (IIH), obesity and different hormonal states. The aim of this study was to characterize the endocrine profile in women with IIH. Methods: This is a data-based study of 51 IIH patients. We measured anthropometric parameters and assessed hormonal profile including cortisol, testosterone, bioavailable testosterone (BT), prolactin, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, insulin, aldosterone, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Pearson or Spearman rank correlation for non-normally distributed variables were calculated to evaluate the relation among the anthropometric measurements: age, body mass index (BMI), waist and hip circumference and waist to hip ratio (WHR) with hormones levels. Results: Seventy-eight percent of the cohort had WHRu2009<u20090.85 and 21.6% had a WHRu2009>u20090.85. Increased levels of testosterone, BT and androstenedione were all positively related to younger age of diagnosis in patient who are diagnosed after the age of 25 (Ru2009=u2009−1.066, −0.845, −0.735, pu2009<u20090.001, =0.024, 0.019, respectively). No correlation was found between any of the analyzed hormones and the duration of the disease, WHR or BMI, except insulin, which was positively related to BMI (Ru2009=u20090.461, pu2009=u20090.001). Conclusions: Increased levels of circulating androgens are associated with earlier age of onset of IIH in women.

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

BackgroundErdheim-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.ObjectivesThe 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.MethodsPatients 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.ResultsSeven patients (five men, two women) were recruited to the study. The median age at presentation was 53u2009years (range: 39 to 62u2009years). The median follow-up time was 36u2009months (range: 1 to 72u2009months). 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.ConclusionsECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.

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

PURPOSEnTo examine anthropometric and maturational characteristics at diagnosis in pediatric idiopathic intracranial hypertension (IIH).nnnDESIGNnRetrospective, international, multisite study.nnnPARTICIPANTSnPediatric patients (2-18 years of age at diagnosis) with IIH.nnnMAIN OUTCOME MEASURESnBody mass index (BMI), height, and weight Z-scores; sexual maturation.nnnMETHODSnCases 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.nnnRESULTSnTwo 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 (Pearsons correlation coefficient, 0.50; 95% confidence interval [CI], 0.30-0.66; P < 0.001; nxa0= 72), and in girls, a weak association was noted (Pearsons correlation coefficient, 0.34; 95% CI, 0.20-0.47; P < 0.001; nxa0= 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 (Pxa0= 0.002 in girls and Pxa0= 0.02 in boys). Data on Tanner staging, menarchal status, or both were available in 25% of cases (nxa0= 57/233). Prepubertal participants (nxa0= 12) had lower average BMI Z-scores (0.95±1.98) compared with pubertal participants (nxa0= 45; 1.92±0.60), but this result did not reach statistical significance (Pxa0=xa00.09).nnnCONCLUSIONSnWith 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.

Automated Cross-Sectional Measurement Method of Intracranial Dural Venous Sinuses

BACKGROUND AND PURPOSE: MRV is an important blood vessel imaging and diagnostic tool for the evaluation of stenosis, occlusions, or aneurysms. However, an accurate image-processing tool for vessel comparison is unavailable. The purpose of this study was to develop and test an automated technique for vessel cross-sectional analysis. MATERIALS AND METHODS: An algorithm for vessel cross-sectional analysis was developed that included 7 main steps: 1) image registration, 2) masking, 3) segmentation, 4) skeletonization, 5) cross-sectional planes, 6) clustering, and 7) cross-sectional analysis. Phantom models were used to validate the technique. The method was also tested on a control subject and a patient with idiopathic intracranial hypertension (4 large sinuses tested: right and left transverse sinuses, superior sagittal sinus, and straight sinus). The cross-sectional area and shape measurements were evaluated before and after lumbar puncture in patients with idiopathic intracranial hypertension. RESULTS: The vessel-analysis algorithm had a high degree of stability with <3% of cross-sections manually corrected. All investigated principal cranial blood sinuses had a significant cross-sectional area increase after lumbar puncture (P ≤ .05). The average triangularity of the transverse sinuses was increased, and the mean circularity of the sinuses was decreased by 6% ± 12% after lumbar puncture. Comparison of phantom and real data showed that all computed errors were <1 voxel unit, which confirmed that the method provided a very accurate solution. CONCLUSIONS: In this article, we present a novel automated imaging method for cross-sectional vessels analysis. The method can provide an efficient quantitative detection of abnormalities in the dural sinuses.

The obesity pattern of idiopathic intracranial hypertension in men

BackgroundIdiopathic 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.MethodsThis 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.ResultsNo 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 (114u2009±u200913 vs. 104u2009±u200916xa0cm; respectively, pu2009<u20090.001). Consequently, waist-to-hip ratio (WHR) was significantly lower in the male IIH cohort (0.88u2009±u20090.08 vs. 0.95u2009±u20090.12; pu2009<u20090.001). 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 (102u2009±u200919xa0cm vs. 95u2009±u200913xa0cm, pu2009<u20090.001; 0.88u2009±u20090.08 vs. 0.78u2009±u20090.06, pu2009<u20090.001, respectively). All these results maintained after adjustment for age and BMI.ConclusionsThis 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.