Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency.

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.

Good Visual Outcomes After Pituitary Tumor Surgery Are Associated With Increased Visual Cortex Functional Connectivity.

BACKGROUND: Patients presenting with visual impairment secondary to pituitary macroadenomas often experience variable recovery after surgery. Several factors may impact visual outcomes including the extent of neuroaxonal damage in the afferent visual pathway and cortical plasticity. Optical coherence tomography (OCT) measures of retinal structure and resting-state functional MRI (rsfMRI) can be used to evaluate the impact of neuroaxonal injury and cortical adaptive processes, respectively. The purpose of this study was to determine whether rsfMRI patterns of functional connectivity (FC) distinguish patients with good vs poor visual outcomes after surgical decompression of pituitary adenomas. METHODS: In this retrospective cohort study, we compared FC patterns between patients who manifested good (GO) vs poor (PO) visual outcomes after pituitary tumor surgery. Patients (n = 21) underwent postoperative rsfMRI a minimum of 1 year after tumor surgery. Seed-based connectivity of the visual cortex (primary [V1], prestriate [V2], and extrastriate [V5]) was compared between GO and PO patients and between patients and healthy controls (HCs) (n = 19). Demographics, visual function, and OCT data were compared preoperatively and postoperatively between patient groups. The threshold for GO was visual field mean deviation equal or less than -5.00 dB and/or visual acuity equal to or better than 20/40. RESULTS: Increased postoperative FC of the visual system was noted for GO relative to PO patients. Specifically, good visual outcomes were associated with increased connectivity of right V5 to the bilateral frontal cortices. Compared with HCs, GO patients showed increased connectivity of V1 and left V2 to sensorimotor cortex, increased connectivity of right and left V2 to medial prefrontal cortex, and increased connectivity of right V5 the right temporal and frontal cortices. CONCLUSIONS: Increased visual cortex connectivity is associated with good visual outcomes in patients with pituitary tumor, at late phase of recovery. Our findings suggest that rsfMRI does distinguish GO and PO patients after pituitary tumor surgery. This imaging modality may have a future role in characterizing the impact of cortical adaptation on visual recovery.

Hemorrhagic Intracranial Cavernoma Presenting as a Homonymous Horizontal Sectoranopia.

ABSTRACT: Hemorrhagic lateral geniculate nucleus (LGN) insults are rare but have been reported in association with tumors, vascular malformations, and trauma. The localization of LGN lesions is facilitated by recognition of pathognomonic visual field defects. A 21-year old woman developed a sudden onset painless left homonymous horizontal sectoranopia. Magnetic resonance imaging revealed a hemorrhagic cavernous malformation of the right temporal lobe. Optical coherence tomography (OCT) and Humphrey perimetry findings localized the lesion to the right LGN. Specifically, OCT testing revealed a right homonymous sectoranopia pattern of hemi-retinal macular ganglion layer-inner plexiform layer (mGCIPL) thinning contralateral to the left sided visual field defect. The OCT pattern reflected retrograde neuroaxonal degeneration from the right LGN lesion. This case highlights a unique pattern of mGCIPL thinning characteristic for a posterior lateral choroidal artery injury, affecting the LGN. These findings illustrate how functional eloquence correlates with topographical elegance in the afferent visual pathway.

Functional-Optical Coherence Tomography: A Non-invasive Approach to Assess the Sympathetic Nervous System and Intrinsic Vascular Regulation.

Sympathetic nervous system dysregulation and vascular impairment in neuronal tissue beds are hallmarks of prominent cardiorespiratory diseases. However, an accurate and convenient method of assessing SNA and local vascular regulation is lacking, hindering routine clinical and research assessments. To address this, we investigated whether spectral domain optical coherence tomography (OCT), that allows investigation of retina and choroid vascular responsiveness, reflects sympathetic activity in order to develop a quick, easy and non-invasive sympathetic index. Here, we compare choroid and retina vascular perfusion density (VPD) acquired with OCT and heart rate variability (HRV) to microneurography. We recruited 6 healthy males (26 ± 3 years) and 5 healthy females (23 ± 1 year) and instrumented them for respiratory parameters, ECG, blood pressure and muscle sympathetic nerve microneurography. Choroid VPD decreases with the cold pressor test, inhaled hypoxia and breath-hold, and increases with hyperoxia and hyperpnea suggesting that sympathetic activity dominates choroid responses. In contrast, retina VPD was unaffected by the cold pressor test, increased with hypoxia and breath hold and decreases with hyperoxia and hyperpnea, suggesting metabolic vascular regulation dominates the retina. With regards to integrated muscle sympathetic nerve activity, HRV had low predictive power whereas choroid VPD was strongly (inversely) correlated with integrated muscle sympathetic nerve activity (R = -0.76; p < 0.0001). These data suggest that Functional-OCT may provide a novel approach to assess sympathetic activity and intrinsic vascular responsiveness (i.e., autoregulation). Given that sympathetic nervous system activity is the main determinant of autonomic function, sympathetic excitation is associated with severe cardiovascular/cardiorespiratory diseases and autoregulation is critical for brain health, we suggest that the use of our new Functional-OCT technique will be of broad interest to clinicians and researchers.

New Ways of "Seeing" the Mechanistic Heterogeneity of Multiple Sclerosis Plaque Pathogenesis.

BACKGROUND: Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments. EVIDENCE ACQUISITION: A constellation of inflammation, ion channel derangements, bioenergetic supply: demand mismatches within the intra-axonal compartment, and alterations in the dynamics and oximetry of blood flow in CNS tissue compartments are observed in MS. These findings have raised questions regarding how histopathologic heterogeneity may influence the diverse clinical spectrum of MS; and, accordingly, how individual treatment needs vary from 1 patient to the next. RESULTS: We are now on new scaffolding in MS; one that promises to translate key clinical and laboratory observations to the application of emerging patient-centered therapies. CONCLUSIONS: This review highlights our current knowledge of the underlying disease mechanisms in MS, explores the inflammatory and neurodegenerative consequences of tissue damage, and examines physiologic factors that contribute to bioenergetic homeostasis within the CNS of affected patients.

Vitamin D in multiple sclerosis and central nervous system demyelinating disease--a review.

BACKGROUND: The role of vitamin D as both a risk factor and a disease modifier in multiple sclerosis (MS) has a storied history with ongoing accumulation of supportive convergent evidence from animal data, clinical studies and trials, and biomarkers of disease. EVIDENCE ACQUISITION: A detailed review of the published literature ranging from in vivo immune studies to human clinical studies of epidemiology, physiology, immunology, clinical, and radiological markers was undertaken. RESULTS: There is compelling evidence that vitamin D is not only a risk factor for central nervous system (CNS) demyelinating disease (namely MS) but also seems to modify both the inflammatory and neurodegenerative elements of the disease, with large-scale treatment trials underway. The authors also address questions of interest that remain unanswered. CONCLUSIONS: Vitamin D is an important contributor and modifiable risk factor in CNS demyelinating disease. Further work will determine whether it is also neuroprotective and if such benefits will apply to other inflammatory and degenerative neurological diseases.

Optical coherence tomography technologies: which machine do you want to own?

Optical coherence tomography (OCT) has evolved over the past decade to become one of the most important ancillary tests in ophthalmic practice. This noninvasive ocular imaging technique provides high-resolution, cross-sectional images of the retinal nerve fiber layer (RNFL), macular region, ganglion cell layer, and optic nerve head. With OCT, we can learn much about axonal-neuronal integrity in the anterior aspect of the afferent visual pathway and gain insights about mechanisms of brain injury in various central nervous system disorders.

Optical coherence tomography in the diagnosis and management of optic neuritis and multiple sclerosis.

Optic neuritis (ON) is an inflammatory optic nerve injury, which is strongly associated with multiple sclerosis (MS). Optical coherence tomography (OCT) has the potential to provide a reliable means of capturing axonal deficits, which can be paired to tests of visual function to provide a structural-functional paradigm of brain injury. In this respect, the eye provides a unique view into the effects of central nervous system inflammation, which may enhance the understanding of disease mechanisms that contribute to neurological disability in MS. This review addresses the published experience with OCT in the diagnosis and treatment of patients with ON and MS, and discusses the applications of OCT in ongoing clinical trials. The potential gains and limitations of spectral-domain OCT as an evolving technology and surrogate marker of axonal brain injury are also discussed.

Neuroimaging in neuro-ophthalmology.

The modern imaging era has introduced a variety of techniques that aid in the evaluation of complex neurologic problems. To optimize the yield of neuroimaging the clinician must, first and foremost, determine the nature of the neuro-ophthalmic disorder; and then localize the lesion. Once the localization of the neuro-ophthalmic problem is understood, the optimal imaging modality can be directed toward the anatomic region of interest. In this article the approach to neuroimaging is discussed, with emphasis on the anatomic localization of lesions affecting afferent and efferent visual function.