Victoria S. Pelak

New low-contrast vision charts: reliability and test characteristics in patients with multiple sclerosis.

The quantitative assessment of visual function in multiple sclerosis (MS) clinical trials has been limited to Snellen visual acuity. The purpose of this study was to examine the inter-rater reliability and test characteristics of a new visual outcome measure, the Low-Contrast Sloan Letter Charts, in patients with MS and visually-asymptomatic volunteers. Contrast letter acuity scores (letter scores) were measured at each of four contrast levels (100, 5, 1.25 and 0.6%) by two independent raters. Inter-rater agreement was described with the intraclass correlation coefficient (ICC) and comparison of mean scores. Excellent inter-rater agreement (ICC=0.86-0.95) was demonstrated at each contrast level among MS patients (n=100) and visually-asymptomatic volunteers (n=33). Average letter scores at the lowest contrast level (0.6%) were highly variable in the MS group, even among patients with visual acuities of 20/20 or better, and among those who required no assistance for ambulation. Low-Contrast Sloan Letter Chart testing is a highly reliable method of visual assessment, and provides information on an aspect of neurologic impairment in MS which is not captured by Snellen visual acuity or ambulation status. This new method demonstrates excellent potential as a visual function outcome measure for future MS clinical trials.

Dural sinus stent placement for idiopathic intracranial hypertension

OBJECT The use of unilateral dural sinus stent placement in patients with idiopathic intracranial hypertension (IIH) has been described by multiple investigators. To date there is a paucity of information on the angiographic and hemodynamic outcome of these procedures. The object of this study was to define the clinical, angiographic, and hemodynamic outcome of placement of unilateral dural sinus stents to treat intracranial venous hypertension in a subgroup of patients meeting the diagnostic criteria for IIH. METHODS Eighteen consecutive patients with a clinical diagnosis of IIH were treated with unilateral stent placement in the transverse-sigmoid junction region. All patients had papilledema. All 12 female patients had headaches; 1 of 6 males had headaches previously that disappeared after weight loss. Seventeen patients had elevated opening pressures at lumbar puncture. Twelve patients had opening pressures of 33-55 cm H(2)O. All patients underwent diagnostic cerebral arteriography that showed venous outflow compromise by filling defects in the transverse-sigmoid junction region. All patients underwent intracranial selective venous pressure measurements across the filling defects. Follow-up arteriography was performed in 16 patients and follow-up venography/venous pressure measurements were performed in 15 patients. RESULTS Initial pressure gradients across the filling defects ranged from 10.5 to 39 mm Hg. Nineteen stent procedures were performed in 18 patients. One patient underwent repeat stent placement for hemodynamic failure. Pressure gradients were reduced in every instance and ranged from 0 to 7 mm Hg after stenting. Fifteen of 16 patients in whom ophthalmological follow-up was performed experienced disappearance of papilledema. Follow-up arteriography in 16 patients at 5-99 months (mean 25.3 months, median 18.5 months) showed patency of all stents without in-stent restenosis. Two patients had filling defects immediately above the stent. Four other patients developed transverse sinus narrowing above the stent without filling defects. One of these patients underwent repeat stent placement because of hemodynamic deterioration. Two of the other 3 patients had hemodynamic deterioration with recurrent pressure gradients of 10.5 and 18 mm Hg. CONCLUSIONS All stents remained patent without restenosis. Stent placement is durable and successfully eliminates papilledema in appropriately selected patients. Continuing hemodynamic success in this series was 80%, and was 87% with repeat stent placement in 1 patient.

Consensus classification of posterior cortical atrophy

A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.

Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI

Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging and frequently represents the prodromal phase of Alzheimers disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group-independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed an increased DMN activity in middle cingulate cortex, medial prefrontal cortex and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus and right angular gyrus. Although MTL volume difference between the two groups was not statistically significant, a decreased activity in left MTL was observed for the aMCI group. Positive correlations between the DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture that correlate with memory function, even before significant MTL atrophy is detectable by structural MRI.

Computerized visual field defects in posterior cortical atrophy

Background and objective: Posterior cortical atrophy (PCA) is a progressive neurodegenerative syndrome that presents with cortical visual dysfunction and relatively preserved memory. Although higher cortical visual syndromes are well known in PCA, visual field defects detected by computerized visual field (CVF) perimetry have not been systematically described. The objective of this study was to describe CVF defects measured by threshold perimetry in PCA. Methods: This was a retrospective case series of patients meeting proposed PCA diagnostic criteria seen in the Neuro-ophthalmology and Neurobehavior Clinics at the University of Colorado during 2002 to 2006. History, examination, neuroimaging, autopsy, and CVF studies were analyzed. Results: Nine of 11 patients who met the criteria for PCA and had CVF testing were included. Seven of the 9 patients had homonymous hemianopia or quadrantanopia, and 2 had bilateral constriction. All patients progressed to dementia. Criteria were met for probable Alzheimer disease (AD) in 7, definite AD in 1, and definite dementia with Lewy bodies associated with AD pathology in 1. Seven of 9 patients had early and prominent complaints of difficulty driving. Conclusions: CVF defects were characterized by homonymous visual field defects or bilateral constriction. Eight of 9 patients progressed to probable or definite AD, but the CVF defects were distinctly different from those in typical AD. This observation probably reflects a posterior shift of cortical pathology to the primary and early secondary visual cortices in PCA. CVF testing should be considered in older patients with unexplained visual complaints, particularly when associated with difficulty driving, which may indicate the possibility of PCA and prompt early neurobehavioral evaluation.

Ocular motility of aging and dementia.

Visual complaints in patients with dementia are varied and attributable to both visual sensory (afferent) and ocular motor (efferent) dysfunction. This review focuses exclusively on the efferent visual dysfunction associated with dementia and aging. It provides a brief overview of the most common ocular motility disturbances associated with dementia, including Alzheimer’s disease, Parkinson’s disease, diffuse Lewy body disease, corticobasal syndrome, progressive supranuclear palsy, frontotemporal lobar degeneration, Creutzfeldt-Jakob disease, and others. An introduction to the six eye movement systems and the terminology associated with the evaluation of each system are reviewed. Assessment of efferent visual function in patients with dementia may be challenging, but familiarity with the potential pathologic eye movement findings in patients with dementia will allow for a focused assessment, diagnosis, and treatment when possible.

Spinal and cranial hypertrophic neuropathy in multiple sclerosis.

Two patients with multiple sclerosis developed symptomatic chronic inflammatory demyelinating polyneuropathy with massive spinal or cranial nerve hypertrophy revealed by neuroimaging. Sural nerve biopsy in one showed only moderate demyelination, axonal loss, and onion‐bulb formation, illustrating dichotomy between severe proximal and milder distal nerve involvement. Patients with coexistent central and peripheral demyelination usually are symptomatic from dysfunction at one site or the other, but not from both. Our patients showed minimal response to steroids, intravenous immunoglobulin, or azathioprine. These cases suggest that the mechanism of disease in symptomatic central and peripheral demyelination may differ from that of disease in only one region, and that optimal therapy in this situation must be explored further. Muscle Nerve, 2005

Nonarteritic anterior ischemic optic neuropathy in a child with optic disk drusen.

Optic disk drusen are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. The clinical course is variable, ranging from stable vision to acute or progressive visual loss. We evaluated a healthy 12-year-old boy with a history of asymptomatic bilateral disk drusen who presented with acute painless unilateral visual loss after hiking to an altitude of 11,000 feet. Findings were consistent with nonarteritic anterior ischemic optic neuropathy.

Determining whether delayed nonarteritic ischemic optic neuropathy associated with cataract extraction is a true entity

PURPOSE: To evaluate cases of delayed nonarteritic anterior and posterior ischemic optic neuropathy after cataract extraction and to evaluate the need for centralized prospective reporting of nonarteritic ischemic optic neuropathy after cataract extraction. SETTING: Neuro‐ophthalmology Clinics, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, Denver, Colorado, USA. METHODS: A retrospective review of all patients referred to the Neuro‐ophthalmology Divisions, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, from January 2001 to October 2005 was performed. All patients with a diagnosis of nonarteritic anterior or posterior ischemic optic neuropathy were identified. Patients with ischemic optic neuropathy that occurred between 2 months and 12 months after cataract extraction were selected for evaluation. RESULTS: Six eyes with nonarteritic ischemic optic neuropathy that occurred 2 to 6 months after cataract extraction in 4 patients (2 bilateral nonarteritic ischemic optic neuropathy) and 1 eye with nonarteritic ischemic optic neuropathy that occurred after 6 months in 1 patient were identified. One patient had nonarteritic ischemic optic neuropathy in 1 eye 3 months after cataract extraction and 4 years later had nonarteritic ischemic optic neuropathy in the fellow eye 5 months after cataract extraction. Follow‐up after the last cataract extraction was 1 to 3 years for all patients. CONCLUSIONS: Although an association between cataract extraction and delayed nonarteritic anterior and posterior ischemic optic neuropathy has been suggested, current data do not support a causal relationship. In addition, the window of postoperative susceptibility for delayed ischemic optic neuropathy after cataract extraction is unclear.

A preliminary study of functional abnormalities in aMCI subjects during different episodic memory tasks.

Functional magnetic resonance imaging (fMRI) is an important imaging modality to understand the neurodegenerative course of mild cognitive impairment (MCI) and early Alzheimers disease (AD), because the memory dysfunction may occur before structural degeneration is obvious. In this research, we investigated the functional abnormalities of subjects with amnestic MCI (aMCI) using three episodic memory paradigms that are relevant to different memory domains in both encoding and recognition phases. Both whole-brain analysis and region-of-interest (ROI) analysis of the medial temporal lobes (MTL), which are central to the memory formation and retrieval, were used to compare the efficiency of the different memory paradigms and the functional difference between aMCI subjects and normal control subjects. We also investigated the impact of using different functional activation measurements in ROI analysis. This pilot study could facilitate the use of fMRI activations in the MTL as a marker for early detection and monitoring progression of AD.