A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease-Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson's disease (PD). A cohort study of GBA carriers between 40-75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40-74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7-33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14-32%), Unified Parkinson's Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2-26.4%), smell assessment (12.4%, 95% CI 6.6-20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7-19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as "abnormal". Then we calculated the percentage of "abnormal" tests for each subject; the median (range) was 4.55 (0-43.5%). Twenty-two subjects had more than 15% "abnormal" tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD

Injury Induced by Chemical Warfare Agents: Characterization and Treatment of Ocular Tissues Exposed to Nitrogen Mustard

PURPOSE. Mustard agents are highly toxic and abundant warfare chemicals, primarily affecting ocular tissues, with no specific treatment antidote. The purpose of the present study was to examine the efficacy of novel metallocomplexes, known to inhibit the formation of highly reactive free radicals, to reduce ocular injury induced by nitrogen mustard (NM). METHODS. One eye in each of 72 rabbits was exposed to 1% to 2% NM. Topical treatment with eye drops of a metallocomplex-either zinc-or gallium-desferrioxamine (Zn/DFO and Ga/DFO)-was compared with treatment with saline, zinc (chloride), or DFO alone. Examiners masked to the treatment groups assessed the extent of ocular injury and the response to treatment using clinical, histologic, and biochemical criteria. RESULTS. Exposure to NM followed by administration of carrier alone (saline) caused severe and long-lasting injury to ocular anterior segment structures. Treatment with either Zn/DFO or Ga/DFO yielded marked protection (52%-64%), including faster healing of corneal epithelial erosions, less scarring and neovascularization, decreased inflammation in the anterior chamber, better maintenance of intraocular pressure, and less severe changes in the iris and lens. These were also associated with better preservation of systemic antioxidant status. Zinc or DFO alone afforded lower levels of protection. No toxic effects of these complexes were observed. CONCLUSIONS. It is suggested that Zn/DFO or Ga/DFO, by virtue of their enhanced ability to infiltrate cells and inhibit transition metal-dependent formation of free radicals through the combined push-pull mechanism, be considered as a basis for treatment of mustard injuries. (Invest Ophthalmol Vis Sci

Visual acuity improvement in children with albinism beyond the first decade of life.

PurposeTo determine if visual maturation continues beyond the first decade of life in children with albinism and whether this is related to albinism type, presence of nystagmus, eye muscle surgery or refractive errors.DesignCase series based on retrospective study of children with confirmed genetic diagnosis of albinism.MethodsClinical data were obtained from medical files of children examined during school years, including albinism type, visual acuity, eye muscle surgery, nystagmus, and others on different visits (Visit 1: ages 7-9; Visit 2: ages: 10-12; Visit 3: ages 13-16; Visit 4: ages >16).ResultsSeventy-five children with albinism were included in the study. Patients were divided into different groups according to the albinism type including OCA1A: 17; OCA1B: 28; OCA2: 26; HPS: 3; OCA4: 1. Follow-up ranged from 3-13 years. Progressive visual acuity improvement was seen in all three main groups. T-test paired samples showed a statistically significant improvement when comparing vision from Visit 1 and Visit 3 in both OCA1A and OCA2 groups, with a mean vision improvement of 2 lines. There was no correlation between visual improvement and refractive error, eye muscle surgery or nystagmus.ConclusionAn improved visual performance was seen in a large percentage of children with albinism during the second decade of life. The reason for this late improvement in vision is not clear but may be related to late foveal maturation or improvement in nystagmus with time. This information is useful for clinicians of these patients and when counseling parents

TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations

International audiencePrecise genetic and phenotypic characterization of congenital stationary night blindness (CSNB) patients is needed for future therapeutic interventions. The aim of this study was to estimate the prevalence of CSNB in our populations and to study clinical and genetic aspects of the autosomal recessive (AR) form of CSNB. This is a retrospective cohort study of Palestinian and Israeli CSNB patients harboring mutations in TRPM1 underwent comprehensive ocular examination. Genetic analysis was performed using homozygosity mapping and sequencing. 161 patients (from 76 families) were recruited for this study, leading to a prevalence of 1:6210 in the vicinity of Jerusalem, much higher than the worldwide prevalence. 61% of the families were consanguineous with AR inheritance pattern. Biallelic pathogenic TRPM1 mutations were identified in 36 families (72 patients). Two founder mutations explain the vast majority of cases: a nonsense mutation c.880A>T (p.Lys294*) identified in 22 Palestinian families and a large genomic deletion (36,445 bp) encompassing exons 2–7 of TRPM1 present in 13 Ashkenazi Jewish families. Most patients were myopic (with mean BCVA of 0.40 LogMAR) and all had absent rod responses in full field electroretinography. To the best of our knowledge, this is the largest report of a clinical and genetic analysis of patients affected with CSNB due to TRPM1 mutations