Alzheimer's Disease (AD) and mild cognitive impairment (MCI) are associated with widespread changes in brain structure and function, as indicated by magnetic resonance imaging (MRI) morphometry and 18-fluorodeoxyglucose position emission tomography (FDG PET) metabolism. Nevertheless, the ability to differentiate between AD, MCI and normal aging groups can be difficult. Thus, the goal of this study was to identify the combination of cerebrospinal fluid (CSF) biomarkers, MRI morphometry, FDG PET metabolism and neuropsychological test scores to that best differentiate between a sample of normal aging subjects and those with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative. The secondary goal was to determine the neuroimaging variables from MRI, FDG PET and CSF biomarkers that can predict future cognitive decline within each group. To achieve these aims, a series of multivariate stepwise logistic and linear regression models were generated. Combining all neuroimaging modalities and cognitive test scores significantly improved the index of discrimination, especially at the earliest stages of the disease, whereas MRI gray matter morphometry variables best predicted future cognitive decline compared to other neuroimaging variables. Overall these findings demonstrate that a multimodal approach using MRI morphometry, FDG PET metabolism, neuropsychological test scores and CSF biomarkers may provide significantly better discrimination than any modality alone.
The inability of axons to regenerate over long-distances in the central nervous system (CNS) limits the recovery of sensory, motor, and cognitive functions after various CNS injuries and diseases. Although pre-clinical studies have identified a number of manipulations that stimulate some degree of axon growth after CNS damage, the extent of recovery remains quite limited, emphasizing the need for improved therapies. Here, we used traumatic injury to the mouse optic nerve as a model system to test the effects of combining several treatments that have recently been found to promote axon regeneration without the risks associated with manipulating known tumor suppressors or oncogenes. The treatments tested here include TPEN, a chelator of mobile (free) zinc (Zn); shRNA against the axon growth-suppressing transcription factor Klf9; and the atypical growth factor oncomodulin combined with a cAMP analog. Whereas some combinatorial treatments produced only marginally stronger effects than the individual treatments alone, co-treatment with TPEN and Klf9 knockdown had a substantially stronger effect on axon regeneration than either one alone. This combination also promoted a high level of cell survival at longer time points. Thus, Znchelation in combination with Klf9 suppression holds therapeutic potential for promoting axon regeneration after optic nerve injury, and may also be effective for treating other CNS injuries and diseases.
BACKGROUND: Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss. METHODS: Case series and review of the literature. RESULTS: We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy. CONCLUSIONS: Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.
BACKGROUND: Prosthetic replacement of the ocular surface ecosystem (PROSE) treatment is an effective, nonsurgical therapeutic option for patients with ocular surface disease related to cranial nerve deficits secondary to skull base tumor resection. METHODS: This case series describes the impact of PROSE treatment in patients with symptomatic exposure keratopathy or neurotrophic keratitis after skull base tumor surgery. RESULTS: All patients improved symptomatically and functionally with PROSE treatment, and have had sustained improvement for as long as 3 years. CONCLUSIONS: In postneurosurgical cases in which neurologic function may recover, PROSE treatment offers a safe, nonsurgical treatment option to support the ocular surface during the period of observation awaiting neurologic recovery.
Growing evidence demonstrates dramatic structural and functional neuroplastic changes in individuals born with early-onset blindness. For example, cross-modal sensory processing at the level of the occipital cortex appears to be associated with adaptive behaviors in the blind. However, detailed studies examining the structural properties of key white matter pathways in other regions of the brain remain limited. Given that blind individuals rely heavily on their sense of hearing, we examined the structural properties of two important pathways involved with auditory processing, namely the uncinate and arcuate fasciculi. High angular resolution diffusion imaging (HARDI) tractography was used to examine structural parameters (i.e., tract volume and quantitative anisotropy, or QA) of these two fasciculi in a sample of 13 early blind individuals and 14 normally sighted controls. Compared to controls, early blind individuals showed a significant increase in the volume of the left uncinate fasciculus. A small area of increased QA was also observed halfway along the right arcuate fasciculus in the blind group. These findings contribute to our knowledge regarding the broad neuroplastic changes associated with profound early blindness.
Purpose: Precise measurements of visual fixation and its instability were recorded during optical coherence tomography (OCT) as a marker of neural network dysfunction in multiple sclerosis (MS), which could be used to monitor disease progression or response to treatment. Methods: A total of 16 MS patients and 26 normal subjects underwent 30 seconds of scanning laser ophthalmoscope (SLO)-based eye tracking during OCT scanning of retinal layer thickness. Study groups consisted of normal eyes, MS eyes without prior optic neuritis (MS wo ON), and MS eyes with prior optic neuritis (MS + ON). Kernel density estimation quantified fixation instability from the distribution of fixation points on the retina. In MS wo ON eyes, fixation instability was compared to other measures of visual and neurologic function. Results: Fixation instability was increased in MS wo ON eyes (0.062 deg2) compared to normal eyes (0.030 deg2, P = 0.015). A further increase was seen for MS + ON eyes (0.11 deg2) compared to MS wo ON (P = 0.04) and normal (P = 0.006) eyes. Fixation instability correlated weakly with ganglion cell layer (GCL) volume and showed no correlation with low-contrast letter acuity, EDSS score, or SDMT score. Conclusions: Fixation instability reflects the integrity of a widespread neural network germane to visual processing and ocular motor control, and is disturbed in MS. Further study of visual fixation, including the contribution of microsaccades to fixation instability, may provide insight into the localization of fixation abnormalities in MS and introduce innovative and easily measured outcomes for monitoring progression and treatment response.
PURPOSE OF REVIEW: We review new applications of optical coherence tomography (OCT) technology in neuro-ophthalmology. We also describe new technologies for visualizing the extracranial vessels in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Newer OCT modalities are expanding the evaluation of the optic disc, and are being applied to a number of neurologic conditions such as demyelinating and neurodegenerative disease. Swept-source OCT and enhanced-depth imaging OCT are refining the fine-grained analysis of the optic nerve head in the diagnosis of papilledema and optic nerve drusen. OCT-angiography is opening up new avenues to the study of the vasculature of the optic nerve head and its disorders, including ischemic optic neuropathy. Newer technologies in the diagnosis of GCA include vascular ultrasound, magnetic resonance imaging (MRI) of the extracranial vasculature and PET imaging of the large vessels. SUMMARY: OCT and several of its derivations are advancing diagnosis, and in some cases prognostication, in a variety of inflammatory, ischemic and compressive optic neuropathies. These technologies hold potential in the laboratory as well, yielding insights into the mechanisms of a variety of neurological conditions. In addition, further developments in MRI and ultrasonography techniques are shaping the approach to the diagnosis of GCA.
AIMS: We set out to determine the optical coherence tomographic angiography (OCT-A) characteristics of arteritic anterior ischaemic optic neuropathy (AAION) in the context of giant cell arteritis (GCA). METHODS: This is an observational case series of four patients with AAION secondary to GCA, three with unilateral AAION and one with bilateral AAION. We reviewed the charts, fundus photography, visual fields, fluorescein angiography (FA) and OCT-A images for all patients to identify a unifying theme in a range of AAION clinical severity. Imaging of two healthy control eyes from two patients of similar age to the patients in our series were used for comparison. RESULTS: Superficial peripapillary capillary dilation was seen in eyes with acute AAION. It was also noted in the fellow eyes of two patients. Retinal capillary perfusion defects corresponded to visual field loss. Dense optic disc oedema and cotton-wool spots imparted blockage effects. OCT-A laminar analysis did not highlight the choroidal/choriocapillaris perfusion defects seen on FA in two patients. Follow-up OCT-A was obtained in two patients and revealed progression to superficial peripapillary capillary attenuation that corresponded with visual field loss. CONCLUSIONS: There are acute and chronic vascular changes in AAION that are detectable by OCT-A that correspond with visual function. Though the microvascular changes seen in GCA and AAION are not specific, the nearly ubiquitous findings among preclinical and clinically affected eyes in this series of patients with GCA support OCT-A as a potentially useful adjunctive diagnostic test in the work-up of ambiguous cases of suspected ischaemic optic neuropathy.
Superior oblique myokymia (SOM) is a rare condition of unclear etiology. We discuss the history, etiology, clinical features, differential diagnoses, management and prognosis of SOM. We conducted a meta-analysis of all 116 cases published since SOM was first described in 1906. The age at examination was 17-72 years (mean 42 years.) There was a right-sided preponderance in 61% of cases (P < 0.02) that was statistically significant in females (63%, P < 0.04) but not in males (59%, P = 0.18). The pathophysiology of SOM may be neurovascular compression and/or ephaptic transmission. Although various pharmacological and surgical approaches to SOM treatment have been proposed, the rarity of the condition has made it impossible to conduct clinical trials evaluating the safety and efficacy of these approaches. Recently, topical beta-blockers have managed SOM symptoms in a number of cases, including the first case treated with levobunolol. Systemic medications, strabismus surgery, and neurosurgery have been used to control symptoms, with strabismus surgery carrying a moderate risk of post-operative diplopia in down-gaze. While there is no established treatment for SOM, we encourage clinicians to attempt topical levobunolol therapy before considering systemic therapy or surgery.