Multi-Criterial Model for Weighting Biological Risk Factors in Multiple Sclerosis: Clinical and Health Insurance Implications.

The etiology of Multiple Sclerosis (MS) remains undetermined. Its pathogenic risk factors are thought to play a negligible role individually in the development of the disease, instead assuming a pathogenic role when they interact with each other. Unfortunately, the statistical weighting of this pathogenic role in predicting MS risk is currently elusive, preventing clinical and health insurance applications. Here, we aim to develop a population-based multi-criterial model for weighting biological risk factors in MS; also, to calculate the individual MS risk value useful for health insurance application. Accordingly, among 596 MS patients retrospectively assessed at the time of diagnosis, the value of vitamin D < 10 nm/L, BMI (Body Mass Index) < 15 Kg/m2 and >30 Kg/m2, female sex, degree of family kinship, and the range of age at onset of 20-45 years were considered as biological risk factors for MS. As a result, in a 30-year-old representative patient having a BMI of 15 and second degree of family kinship for MS, the major developmental contributor for disease is the low vitamin D serum level of 10 nm/L, resulting in an MS risk of 0.110 and 0.106 for female and male, respectively. Furthermore, the Choquet integral applied to uncertain variables, such as biological risk factors, evidenced the family kinship as the main contributor, especially if coincident with the others, to the MS risk. This model allows, for the first time, for the risk stratification of getting sick and the application of the health insurance in people at risk for MS.

Fluphenazine-Induced Neurotoxicity with Acute Almost Transient Parkinsonism and Permanent Memory Loss: Lessons from a Case Report.

We report the singular case of a 31-year-old woman who developed very serious Fluphenazine-induced parkinsonism over a few days due to a doubly incongruent drug prescription by indication and dosage having been applied to a healthy subject over one week instead of seven months. Unlike gradual drug-induced parkinsonism, our patient experienced acute extrapyramidal syndrome (EPS), reaching significant motor and sphincter disability in just a few days, followed by a gradual incomplete recovery over more than six months. In fact, after drug discontinuation, hypomimia and slight left hemi-somatic rigidity with bradykinesia remained, as well as stable non-progressive memory disturbances. Despite bio-humoral and instrumental investigations and DaTScan were negative, MRI post-analysis evidenced a 6.5% loss in brain volume. Specifically, irreversible cortical and sub-cortical grey matter reduction and cerebrospinal fluid space enlargement with spared white matter were found. Our observations suggest that the sudden availability of Fluphenazine results in a kind of plateau effect of parkinsonism presentation, partially reversible due to the neurotoxic drug effect on the cortical and sub-cortical grey matter, resulting in asymmetric EPS and stable memory loss, respectively. Our report confirms the debated neurotoxicity of first-generation neuroleptics and the postulated theory of differential susceptibility to the cytotoxic stressors on the central nervous system.

Microscope-assisted pneumatic retinopexy for the management of primary rhegmatogenous retinal detachment.

PURPOSE: Outcomes of pneumatic retinopexy (PnR) using surgical microscope, wide-angle viewing system, and chandelier endoilluminator (microscope-assisted pneumatic retinopexy) for primary rhegmatogenous retinal detachment (RRD). METHODS: Retrospective study. 43 consecutive eyes with RRD undergoing microscope-assisted PnR surgery (MAPR) were analysed. Inclusion criteria comprehend phakic eyes with single retinal break or a group of breaks in detached retina in the same quadrant above 8- and 4-o'clock meridians. Follow-up was at least 6 months. RESULTS: Of the 43 eyes, a total of 25 (58%) presented preoperatively a single retinal break, 15 (35%) had two retinal breaks in the same quadrant and 3 (7%) presented three or more retinal breaks in the same quadrant. Other retinal breaks not observed preoperatively were discovered intraoperatively in 12 eyes (28%). In 9 (21%) the missed retinal breaks were in the same quadrant as the main diagnosed break(s), while 3 (7%) had missed retinal breaks in a different one. These 3 eyes as no longer adhering to the PnR indication criteria switched intraoperatively to other surgical procedures and were excluded in the reattachment rate results. The total primary reattachment rate with MAPR was achieved in 37 eyes (92.5%). No significant BCVA changes were observed postoperatively. CONCLUSION: MAPR is an effective and safe surgical option, it allows to work with both hands free and provides an adequate visualization of the retina during the procedure minimizing the risk of missed retinal breaks potentially leading to surgical failure.

Changes in Brain Volumes Are Relevant during Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: Lessons from a Case Report.

This is a case report concerning a Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) with cerebellar localization and wakefulness disturbances. Awakening and clinical improvement dramatically occurred as soon as the immune reconstitution inflammatory syndrome (IRIS) took place, being it mild in nature and colocalizing with the PML lesion. In these ideal experimental conditions, we applied brain magnetic resonance imaging post-analysis in order to know changes in brain volumes underlying the pathological process over the infection period. White matter volume increased with a decrease in grey matter during IRIS. Conversely, we found a constant increase in cerebrospinal fluid volume throughout the duration of PML, suggesting a widespread abiotrophic effect, far from the lesion. Furthermore, brain parenchymal fraction significantly decreased as expected while the total brain volume remained stable at all times. Neurodegeneration is the main contributor to the steady disability in Natalizumab-associated PML. This process is thought to be widespread and inflammatory in nature as well as sustained by IRIS and humoral factors derived from the PML lesion.

Dementia-Associated Compulsive Singing (DACS): Presentation of Unpublished Clinical Cases Miniseries.

Dementia-associated compulsive singing (DACS) is a neurotransmettitorial-based behavioral disturbance, characterized by an unabating melodic expression, occurring in patients that suffer from evolved dementia. Previously described only as a "punding" aspect of the dopamine dysregulation syndrome (DDS) in the Parkinson's disease (PD), compulsive singing has now been described, for the first time, in four non-PD patients effectively treated with Haloperidol or Quetiapine. Unlike the DDS-associated conditions, in our cases DACS is not pharmacologically induced, being that all patients were L-dopa-free. We detected a diffuse hyperintensity of the white matter and brain atrophy, with insular shrinkage as well as ventricular system and/or sub-arachnoid space enlargement in our DACS patients. Furthermore, similarly to the other behavioral symptoms of dementia, DACS also seems to be correlated to the degree of cognitive and functional impairment, rather than its subtype. In conclusion, DACS is a non-cognitive, unpublished clinical aspect of evolved dementia, which is interesting due to the involvement of the extra-nigral dopaminergic system, resulting in an unabating altered behavior, but also to the enrichment of our knowledge in the involutional diseases of the central nervous system and their physiopathological manifestations.

Standardized Flanged Intrascleral Intraocular Lens Fixation with the Double-Needle Technique for Cataract Luxation in the Vitreous Chamber during Phacoemulsification.

PURPOSE: To assess the visual and refractive outcome of immediate intraoperative vitrectomy and intrascleral intraocular lens implantation using a "standardized" sutureless Yamane technique during cataract luxation in the vitreous chamber as a complication of phacoemulsification. DESIGN: A prospective, interventional, consecutive case series. MATERIALS AND METHODS: Twelve patients underwent vitrectomy and intrascleral intraocular lens fixation using a standardized Yamane technique as the primary procedure during complicated phacoemulsification. Patients were evaluated preoperatively and 6 months postoperatively for best-corrected distance visual acuity, correspondence to the preoperative refractive target in the spherical equivalent, endothelial cell count, and complications. RESULTS: Mean preoperative best-corrected visual acuity was 1.16 ± 0.3 logarithm of the minimum angle of resolution (logMAR), the endothelial cell count was 1910.5 ± 297.64, and target refraction at baseline was -0.197 ± 0.087. Postoperatively, best-corrected visual acuity was significantly improved; the mean value was 0.05 logMAR ± 0.06. Mean baseline target refraction in the spherical equivalent was -0.20 ± -0.09 (range: -0.08 to -0.37), and mean final refraction was -0.44 ± -0.14 (range: -0.25 to -0.75) with no significant difference (p=0.87). No complication was registered intra- and postoperatively. CONCLUSION: Standardization of the Yamane technique seemed a valuable option for patients who had complicated phacoemulsification to achieve a predictable refractive outcome. Synopsis. The predictable refractive outcome could be achieved with the immediate standardized Yamane technique in patients with intraoperative cataract luxation in the vitreous chamber during phacoemulsification.

Unusual Case of Indolent Choroidal Alterations Mimicking Neurofibromatosis Type 1.

Indolent, non-progressive choroidal alterations can be strongly suggestive of neurofibromatosis type 1 (NF1) but are also rarely of unknown aetiology. A 63-year-old man presented for a routine examination. Comprehensive ophthalmological examination and retinal imaging was performed. Visual acuity was 20/20. The anterior segment and fundus were unremarkable. Near-infrared reflectance (NIR) with spectral-domain optical coherence tomography showed unilateral hyperreflective areas in the left posterior pole, corresponding to choroidal nodules on enhanced depth imaging and hypofluorescent areas on indocyanine green angiography. Dermatological evaluation and genetic testing for NF1 were negative. Chest computed tomography, liver function, HLA-A29, and angiotensin-converting enzyme level were negative. The patient has remained in good health and the choroidal alterations have remained non-progressive for 3 years. Choroidal alterations observed with NIR could be a manifestation of somatic mosaicism or a variation of a new unclassified correlated condition that may be better elucidated in the future, given the use of novel imaging techniques that are currently available in ophthalmology.