Alfred L. Ochs

Retinopathy after tilorone hydrochloride.

Two patients, a 34-year-old woman and a 50-year-old woman, received tilorone HCl, an experimental antitumor drug. After taking the drug orally (total dose, 152 g), the first patient developed corneal subepithelial infiltrates and toxic retinopathy characterized by fine pigment mottling of the peripheral fundus and macula with mild arteriolar narrowing. Although visual acuity was 6/6 (20/20) throughout treatment, Goldmann perimetry showed marked peripheral constriction of the visual fields and results of an electroretinogram and an electro-oculogram were abnormal. After taking the drug orally (total dose, 189 g), the second patient developed corneal subepithelial infiltrates, severe bilateral arteriolar narrowing, and mild pigment mottling of the macula. ERG and EOG were moderately attenuated. Visual fields by Goldman perimetry were within normal limits. Tilorone HCl, like chloroquine, may be an antioxidant that affects the free radical scavenging mechanism of the retinal pigment epithelium. Extensive testing should be done on all patients taking tilorone HCl in order to detect the initial manifestations of retinopathy.

Man Versus Machine: Comparison of Radiologists’ Interpretations and NeuroQuant® Volumetric Analyses of Brain MRIs in Patients With Traumatic Brain Injury

NeuroQuant® is a recently developed, FDA-approved software program for measuring brain MRI volume in clinical settings. The purpose of this study was to compare NeuroQuant with the radiologists traditional approach, based on visual inspection, in 20 outpatients with mild or moderate traumatic brain injury (TBI). Each MRI was analyzed with NeuroQuant, and the resulting volumetric analyses were compared with the attending radiologists interpretation. The radiologists traditional approach found atrophy in 10.0% of patients; NeuroQuant found atrophy in 50.0% of patients. NeuroQuant was more sensitive for detecting brain atrophy than the traditional radiologists approach.

NeuroQuant® Revealed Hippocampal Atrophy in a Patient With Traumatic Brain Injury

Case Report At the time of the accident, he hit his occiput and suffered whiplash. He was dazed but did not lose consciousness. He had posttraumatic amnesia, headache, neck pain, and dizziness. In the emergency room, his Glasgow Coma Scale score was 15/15. Over the following days and weeks, he had multiple persistent neuropsychiatric symptoms, including distractibility, impaired short-term and long-term memory, impaired visuospatial abilities, insomnia, fatigue, and blurry vision. Neuropsychological testing confirmed impairments in memory and other cognitive abilities. Nine months after the accident, an MRI of the brain was interpreted in the traditional manner (that is, by visual inspection of the images) by the radiologist as showing two nonspecific T2 hyperintensities in the left frontal lobe. NeuroQuant volumetric analysis of the same MRI data revealed that total hippocampal volume was 4.37 cm, which was 0.29% of intracranial volume, falling below the first percentile, as compared with an age-matched normal-control group. The patient continued to work full-time at a job he had held for many years; however, his functioning was significantly impaired.

Clinical Significance of Transient Visual Phenomena in the Elderly

To evaluate the significance of transient visual phenomena in the elderly patient, a retrospective study of 43 patients over 40 years of age (mean, 58) presenting between 1971 and 1982 was conducted. Historical, clinical and diagnostic features were collated and analyzed by computer. The study revealed that 31 patients were diagnosed as migraine and 12 as vertebrobasilar insufficiency based on features identified in this review. Follow-up was obtained in 90% of the patients with a mean follow-up of 2.4 years. In general, prognosis proved to be excellent, with two deaths of cardiac origin and an 81% incidence of remission or symptomatic improvement of the visual events. No retinal or cerebral strokes were observed and TIAs occurred in only 9% of the population. This study suggests that transient visual phenomena in the elderly are benign.

Back to the future: Estimating pre-injury brain volume in patients with traumatic brain injury

INTRODUCTION A recent meta-analysis by Hedman et al. allows for accurate estimation of brain volume changes throughout the life span. Additionally, Tate et al. showed that intracranial volume at a later point in life can be used to estimate reliably brain volume at an earlier point in life. These advancements were combined to create a model which allowed the estimation of brain volume just prior to injury in a group of patients with mild or moderate traumatic brain injury (TBI). This volume estimation model was used in combination with actual measurements of brain volume to test hypotheses about progressive brain volume changes in the patients. METHODS Twenty six patients with mild or moderate TBI were compared to 20 normal control subjects. NeuroQuant® was used to measure brain MRI volume. Brain volume after the injury (from MRI scans performed at t1 and t2) was compared to brain volume just before the injury (volume estimation at t0) using longitudinal designs. Groups were compared with respect to volume changes in whole brain parenchyma (WBP) and its 3 major subdivisions: cortical gray matter (GM), cerebral white matter (CWM) and subcortical nuclei+infratentorial regions (SCN+IFT). RESULTS Using the normal control data, the volume estimation model was tested by comparing measured brain volume to estimated brain volume; reliability ranged from good to excellent. During the initial phase after injury (t0-t1), the TBI patients had abnormally rapid atrophy of WBP and CWM, and abnormally rapid enlargement of SCN+IFT. Rates of volume change during t0-t1 correlated with cross-sectional measures of volume change at t1, supporting the internal reliability of the volume estimation model. A logistic regression analysis using the volume change data produced a function which perfectly predicted group membership (TBI patients vs. normal control subjects). CONCLUSIONS During the first few months after injury, patients with mild or moderate TBI have rapid atrophy of WBP and CWM, and rapid enlargement of SCN+IFT. The magnitude and pattern of the changes in volume may allow for the eventual development of diagnostic tools based on the volume estimation approach.

Corrigendum to “Back to the Future: Estimating Pre-Injury Brain Volume in Patients with Traumatic Brain Injury” [NeuroImage 102 (Part 2) (15 November 2014) 565–578]

The purpose of this corrigendum is to describe amistakemade in our previous report (Ross et al., 2014). In developing the brain volume estimation method, the error rate of estimated volume change was miscalculated. As described originally in the paper (Inline Supplementary Methods 10), the error rate of estimated volume change in our normal control group was measured by subtracting estimated brain volume at time nt1 (normal time 1; analogous to patient time 0 = pt0 = the time just before injury) from estimated volume at time nt2 (analogous to pt1, after injury). That was a mistake. The correct method was to subtract estimated volume at nt1 from measured volume at nt2, because this was analogous to how the method was used in patients, that is, by estimating volume at pt0 and measuring it at pt1. As described in the Methods section, the method of making conservative estimates was developed in order to reduce the rate of false positive findings based on the best estimate method. The original, mistaken method did reduce the rate of false positive findings somewhat but did not reduce it enough. So overall, the mistake resulted in an increased rate of false positive findings. This mistake affected only the conservative estimates of brain volume change, which were assessed only in individual patients. It did not affect other analyses, including best estimates of brain volume change assessed in individual patients, or group analyses. Therefore, it did not affect the large majority of the analyses reported in our study. Since the major conclusions of our publication were based on the group analyses, the mistake did not affect them. Specifically, the Abstract, Discussion/Main findings, and Conclusions sections were not affected. Furthermore, the error rates for the cross-sectional (i.e. one point in time) brain volume estimates were correct as originally reported. In other words, the mistaken method affected only estimates of brain volume change (over two points in time). The specific sections of the report affected by the mistake are described below. For Table 4, the rates of abnormal findings for the volume change analyses based on the conservative estimate were inaccurately high. The corrected results are shown in Table 4 (corrected). On page 572