Robert H. I. Blanks

Cephalometric analysis for diagnosis and treatment of obstructive sleep apnea

A detailed cephalometric analysis was conducted on lateral x‐rays from 30 adult patients with obstructive sleep apnea (OSA) and 12 age‐ and sex‐matched controls. Statistical findings show that OSA patients are different from controls in at least five ways: 1. Their tongue and soft palate are significantly enlarged. 2. The hyoid bone is displaced inferiorly. 3. The mandible is normal in size and position (no micrognathia or malocclusion), but the face is elongated by an inferior displacement of the mandibular body. 4. The maxilla is retropositioned and the hard palate elongated. 5. The nasopharynx is normal, but the oropharyngeal and hypopharyngeal airway is reduced in area by an average of 25%, a factor that could produce or enhance OSA symptoms. These data suggest that cephalometric evaluation could be useful when used with head and neck examination, polysomnographic and endoscopic studies to evaluate OSA patients, and to assist with the planning/surgical treatment for improvement of upper airway patency.

Retinal pathology in Alzheimer's disease. I. Ganglion cell loss in foveal/parafoveal retina

Morphometric analysis of the numbers of neurons in the ganglion cell layer (GCL) of the central retina (fovea/foveola/parafoveal retina) in eyes from 9 Alzheimers disease (AD) and 11 age-matched control cases revealed an overall decrease of 25% in total numbers of neurons in AD as compared with control eyes. Detailed analyses of GCL neurons at various eccentricities from the foveola showed that the greatest decrease in neuronal density (43% decrease) occurred in the central 0-0.5 mm (foveal region), while at 0.5-1 mm and at 1-1.5 mm eccentricities, neuronal loss amounted to 24 and 26%, respectively. The temporal region of the central retina appeared most severely affected, with up to 52% decrease in neuronal density near the foveola (central 0-0.5 mm eccentricity). There was close agreement between fellow eyes analyzed separately for three AD and three control cases. Analysis of neuronal sizes showed that all sizes of neurons were similarly affected in AD. In the GCL of control retinas, neurons decreased with age (coefficient of correlation = -0.67), while in AD retinas no such relationship was evident. Since in the central 0-2 mm region of the retina 97% of neurons in the GCL are ganglion cells (while the remaining 3% consist of displaced amacrine cells), these results demonstrate extensive ganglion cell loss in the central retina in AD.

Retinal pathology in Alzheimer's disease. II. Regional neuron loss and glial changes in GCL.

Detailed analyses of neuronal and astrocyte cell numbers in the ganglion cell layer (GCL) of whole-mounted peripheral retinas from 16 Alzheimers disease (AD) and 11 control eyes (11 and 9 cases, respectively) demonstrate extensive neuronal loss throughout the entire retina in AD as compared to control eyes. The observed neuronal loss is most pronounced in the superior and inferior quadrants, ranging between 40 and 49% throughout the midperipheral regions, and reaching 50-59% in the far peripheral inferior retina, while the overall neuronal loss throughout the entire retina amounts to 36.4% (p < 0.004). Although the 16% increase in astrocyte numbers is not significant, the ratio of astrocytes to neurons is significantly higher (82%; p < 0.0008) in AD as compared to normal retina (0.238 +/- 0.070 vs. 0.131 +/- 0.042). These results are strengthened by the close agreement (within +/- 15% of respective means) found between fellow eyes. Analysis of glial fibrillary acidic protein immunoreactivity (GFAP-ir) in sections of retinas from an additional 12 AD and 19 control cases show increased GFAP-ir with more extensive labeling of astrocytes in the GCL as well as increased labeling of Müller cell end-feet and radial processes in AD as compared to control retinas. The extensive loss of neurons documented in these retinas, accompanied by an increased astrocyte/neuron ratio, provides further support for the substantial involvement of the retina in AD.

Afferent projections to the cerebellar flocculus in the pigmented rat demonstrated by retrograde transport of horseradish peroxidase.

SummaryThe horseradish peroxidase (HRP) retrograde transport method was used to identify brainstem afferents to the cerebellar flocculus in the pigmented rat. Injections of the enzyme were made through recording microelectrodes, making it possible to localize the injection site by physiological criteria. Clearly, the largest number of afferents arise from the bilateral vestibular and perihypoglossal nuclei and from the contralateral dorsal cap (of Kooy) of the inferior olive. Additionally, a substantial number arise bilaterally from: (1) the nucleus reticularis tegmenti pontis (NRTP); (2) several of the cranial motor nuclei including the abducens, retrofacial and facial nuclei and the nucleus ambiguus; (3) the rostral part of the lateral reticular nucleus (subtrigeminal nucleus); (4) the raphe pontis and raphe magnus and (5) neurons intercalated among the medial longitudinal fasciculus (MLF) just rostral to the hypoglossal nucleus and another group rostral to the abducens nucleus.The basilar pontine nuclei contained a large number of lightly labeled neurons in all flocculus injections which were discretely located within the dorsolateral, lateral and medial divisions. These areas were labeled bilaterally but with a slight contralateral preponderance. Injection into the flocculus, but involving the adjacent ventral paraflocculus, produced a heavier labeling of pontine neurons with a slightly different distribution. Therefore, we tentatively conclude that the flocculus receives input from these pontine visual centers (dorsolateral, lateral and medial nuclei), perhaps through collateral projections from neurons projecting to the paraflocculus.The present study demonstrates strong similarities between the rat and other species studied (e.g., rabbit, cat, monkey) in terms of the brainstem nuclei projecting to the flocculus. Most noticeable in quantitative terms are the pathways known to mediate vestibular (vestibular and perihypoglossal nuclei) and visual (optokinetic) information (e.g., NRTP). Additionally, we can provide morphological evidence that the midline and paramedian pontine tegmentum, identified in the cat and monkey as containing saccade-related neurons, send large numbers of projections to the rat flocculus. Given these similarities, the rat may be a suitable animal model in which to study the pathways underlying visual-vestibular interaction and saccadic mechanisms in the flocculus.

Planar relationships of the semicircular canals in rhesus and squirrel monkeys

The technique of principal-component analysis was used to define anatomically the semicircular canal planes of the rhesus and squirrel monkeys with respect to the stereotaxic coordinate system. The analyses were performed on a series of points obtained from the dissected osseous labyrinths. A planar equation was defined for each canal plane in the stereotaxic coordinate system and angles were calculated between the 3 ipsilateral canal planes, between synergistic canal pairs and between each canal plane and the stereotaxic planes. The data from both species are similar: the ipsilateral canal planes are nearly orthogonal; synergistic pairs of canal planes are approximately parallel with angles of 2 degrees-12 degrees between pairs in the rhesus monkey and 13 degrees-16 degrees between pairs in the squirrel monkey. The horizontal canal planes form angles of 22 degrees and 18 degrees with the horizontal stereotaxic plane in the rhesus and squirrel monkeys, respectively. A head position of 15 degrees (pitch nose-down) was calculated to produce an optimal head position in both species for maximally stimulating the horizontal canals and minimally stimulating the vertical canals during horizontal angular acceleration. The radii of curvature (R) of the horizontal, anterior and posterior canals were also measured for both species using a calibrated reticle. These measurements indicate that the anterior canal of both species has the largest radius of curvature. This anatomical information is discussed in relation to the available physiological data.

The accessory optic system: basic organization with an update on connectivity, neurochemistry, and function.

The accessory optic system (AOS) is formed by a series of terminal nuclei receiving direct visual information from the retina via one or more accessory optic tracts. In addition to the retinal input, derived from ganglion cells that characteristically have large receptive fields, are direction-selective, and have a preference for slow moving stimuli, there are now well-characterized afferent connections with a key pretectal nucleus (nucleus of the optic tract) and the ventral lateral geniculate nucleus. The efferent connections of the AOS are robust, targeting brainstem and other structures in support of visual-oculomotor events such as optokinetic nystagmus and visual-vestibular interaction. This chapter reviews the newer experimental findings while including older data concerning the structural and functional organization of the AOS. We then consider the ontogeny and phylogeny of the AOS and include a discussion of similarities and differences in the anatomical organization of the AOS in nonmammalian and mammalian species. This is followed by sections dealing with retinal and cerebral cortical afferents to the AOS nuclei, interneuronal connections of AOS neurons, and the efferents of the AOS nuclei. We conclude with a section on Functional Considerations dealing with the issues of the response properties of AOS neurons, lesion and metabolic studies, and the AOS and spatial cognition.

GABAergic neurons comprise a major cell type in rodent visual relay nuclei: an immunocytochemical study of pretectal and accessory optic nuclei*

SummaryThe enzyme glutamic acid decarboxylase (GAD) has been localized in sections of rodent brains (gerbil, rat) using conventional immunocytochemical techniques. Our findings demonstrate that large numbers of GAD-positive neurons and axon terminals (puncta) are present in the visual relay nuclei of the pretectum and the accessory optic system. The areas of highest density of these neurons are in the nucleus of the optic tract (NOT) of the pretectum, the dorsal and lateral terminal accessory optic nuclei (DTN, LTN), the ventral and dorsal subdivisions of the medial terminal accessory optic nucleus (MTNv, MTNd), and the interstitial nucleus of the posterior fibers of the superior fasciculus (inSFp). The findings indicate that 27% of the NOT neurons are GAD-positive and that these neurons are distributed over all of the NOT except the most superficial portion of the NOT caudally. The GAD-positive neurons of the NOT are statistically smaller (65.9 μm2) than the total population of neurons of the NOT (84.3 [j,m2) but are otherwise indistinguishable in shape from the total neuron population. The other visual relay nuclei that have been analyzed (DTN, LTN, MTNv, MTNd, inSFp) are similar in that from 21% to 31% of their neurons are GAD-positive; these neurons are smaller in diameter and are more spherical than the total populations of neurons. The data further show that a large proportion of the neurons in these visual relay nuclei are contacted by GAD-positive axon terminals. It is estimated that approximately one-half of the neurons of the NOT and the terminal accessory optic nuclei receive a strong GABAergic input and have been called “GAD-recipient neurons”. Further, the morphology of the GAD-positive neurons combined with their similar distribution to the GAD-recipient neurons suggest that many of these neurons are acting as GABAergic, local circuit neurons. On the other hand, the large number of GAD-positive neurons in the NOT and MTN (20–30%) in relation to estimates of projection neurons (75%) presents the possibility that some may in fact be projection neurons. The overall findings provide morphological evidence which supports the general conclusion that GABAergic neurons play a significant role in modulating the output of the visually related NOT and terminal accessory optic nuclei.

Cephalometric airway analysis in obstructive sleep apnea syndrome

In obstructive sleep apnea syndrome, polysomnograms characterize the nature and severity of the disorder but, rarely, its specific site. Therefore, 90 patients with documented obstructive sleep apnea were evaluated by cephalometric technique, with special attention paid to the size and position of the soft palate and uvula, volume and position of the tongue, mandibulo‐maxillary relationship, hyoid position, and size of the pharyngeal airway space. Results showed major differences between control patients and patients with obstructive sleep apnea in over 50% (30/52) of the objectively measured indices of the cephalometric airway. Further, many changes in the cephalograms of these patients can be correlated with disease severity.

Projections of the medial terminal nucleus of the accessory optic system upon pretectal nuclei in the pigmented rat

SummaryThe projections of the medial terminal nucleus (MTN) of the accessory optic system (AOS) upon pretectal nuclei have been studied in pigmented rats by means of (i) the anterograde transport of 3H-leucine with the use of light autoradiography and (ii) the retrograde transport of horseradish peroxidase (HRP). Injections of 3H-leucine largely restricted to the MTN and minimally involving adjacent ventral midbrain structures, produced heavy terminal axonal labeling within the ipsilateral nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of the AOS. Terminal labeling was observed in all superficial portions of the NOT, except for a small ventromedial segment in the rostral two thirds and a larger medial segment in the caudal one third of this nucleus. Thus the MTN-NOT projections we describe entirely overlap the retinal-NOT projection and partially overlap the visual cortical-NOT, as reported by others. Within the DTN, the dense terminal fields covered the entire nucleus.After postinjection survival times of 3–7 days, the pattern of axonal labeling showed that the MTNNOT projection consisted of three bundles: (i) a superficial mesencephalic bundle coursing within the superior fasciculus, posterior fibers of the AOS which enters the caudal portions of the NOT and the DTN; (ii) a deep mesencephalic bundle that traversed the midbrain tegmentum dorsolaterally, also reaching the caudal one-half of the NOT and all of the DTN; and (iii) a mesodiencephalic bundle that passed first laterally through midbrain tegmentum and then dorsally through lateral thalamus to enter the rostral one-half of the NOT.Pretectal injections of HRP that invade the NOT and DTN produced retrograde labeling of most (ca. 75%) of the neurons of the ipsilateral MTN, without labeling the adjacent substantia nigra or ventral tegmental area. This finding confirms our autoradiographic data by showing that the MTN provides the major, ventral tegmental projection to the NOT and DTN. The present finding of a MTN-NOT projection, combined with available anatomical and physiological data, suggests that the MTN may play a more significant role in visual-vestibular aspects of oculomotor control than formerly thought.

Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey

Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a and 7b to the basal pontine nuclei were studied using 3H-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei. (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico-pontine pathways arising from parietal cortices target only the basal pontine gray, whereas the NRTP, together with select pontine nuclei, is a recipient of afferents from frontal cortical areas. The present findings implicate the existence of parallel direct and indirect cortico-pontine pathways from frontal motor-related cortices to NRTP and neighboring pontine nuclei.