Characterizing Limbic-Predominant Age-Related TDP-43 Encephalopathy Without Alzheimer's Disease and Lewy Body Dementia in the Oldest Old: A Case Series.

BACKGROUND: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a clinicopathological construct proposed to facilitate studying TDP-43 pathology in older individuals. OBJECTIVE: Our aim was to describe clinical and cognitive characteristics of LATE-NC without Alzheimer's disease neuropathologic change (ADNC) and Lewy body (LB) and to compare this with ADNC and primary age related tauopathy (PART). METHODS: In 364 autopsies of the oldest old of The 90+ Study, we identified those with LATE-NC without ADNC and LB. Control groups were participants with ADNC and PART. RESULTS: Of 31% of participants who had LATE-NC, only 5 (1.4%) had LATE-NC without ADNC and LB, all of whom had tau. These participants had a gradual and progressive cognitive decline. Four (80%) had dementia at death, a rate that was higher than ADNC (50%) and PART (21.7%). Mean duration of cognitive impairment was twice as long in LATE-NC without ADNC and LB (6.2 years) compared to ADNC (2.9 years) and PART (3 years). LATE-NC without ADNC and LB group had a higher prevalence of syncope, depression, and extrapyramidal signs than the ADNC and PART groups. CONCLUSIONS: Despite the high prevalence of LATE-NC, LATE-NC without ADNC and LB was rare in this large oldest-old cohort, highlighting the very high prevalence of multiple pathologic changes in the oldest old. Slowly progressive cognitive decline, ubiquitous memory impairment, history of syncope and depression, and extrapyramidal signs were prominent features among our LATE-NC without ADNC and LB group.

Evaluation of Ocular Side Effects in the Patients on Topiramate Therapy for Control of Migrainous Headache.

INTRODUCTION: Topiramate, a sulfa-derivative monosaccharide, is an antiepileptic drug which is administered in the control of migraine. It is reported to cause various ocular side effects such as visual field defect and myopic shift. To investigate the alterations in refractive error, properties of the cornea and changes in the anterior chamber in patients that receive Topiramate for migraine control. MATERIALS AND METHODS: This is a hospital-based, non-interventional, observational study that is conducted at Imam Hossein Hospital, affiliated to Shahid Beheshti University of Medical Sciences, Department of Neurology, in collaboration with the department of Ophthalmology. Thirty three consecutive patients with the diagnosis of migraine that were candidate for Topiramate therapy were recruited. Patients with history of ocular trauma or surgery, keratoconus, glaucoma, congenital ocular malformations and any history of unexplained visual loss were excluded. After thorough ophthalmic examination, all the patients underwent central corneal thickness (CCT) measurement, and Pentacam imaging (Scheimpflug camera) at the baseline. Various parameters were extracted and used for analysis. Anterior chamber volume (ACV), anterior chamber depth (ACD), and anterior chamber angle (ACA) measurement was performed. These measurements were repeated on day 30(th) and 90(th) after the initiation of Topiramate therapy. According to the normality tests, parameters with normal distribution were analysed using the repeated measures test and the remaining parameters (with non-normal distribution) were analysed using the non-parametric k-sample test. A p-value< 0.05 was considered statistically significant, according to Bonferroni post hoc correction. RESULTS: There were 66 eyes of 33 patients under the diagnosis of migrainous headache, that Topiramate was initiated for headache control, included in the study. The mean value of refractive error had a statistically significant myopic change, from -0.23 diopters (D) at the baseline to -0.61 D at the 90(th) day of follow-up period (p-value < 0.001). Mean CCT was 531.43 µm at the baseline and increased to 534.72 µm at the 30(th) day, and 537.51 µm at the 90(th) day after the administration of Topiramate (p-value=0.001). Mean value of other parameters, ACV, ACD, and ACA, did not reveal statistically significant change. CONCLUSION: Myopic shift and gradually increasing CCT in the patients after Topiramate administration should be considered before any refractive surgery. We found no gradual change in the anterior chamber and angle parameters in our patients in the 90 days of follow up. More studies with a longer duration of follow-up are needed to elucidate dose-dependent ocular manifestations.