The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans.

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

Asymmetric progressive glaucomatous optic neuropathy in a patient with a rare developmental variant of the ophthalmic artery.

PURPOSE: To report a case of a developmental anatomic finding of the ophthalmic artery (OA) in a patient with ipsilateral progressive advanced glaucomatous optic neuropathy and visual field loss. METHODS: A 59-year-old Asian man with normal tension glaucoma had progressive asymmetric visual field loss OD. Magnetic resonance imaging and angiography of the orbit were performed because of continued progression despite medical and surgical intervention. RESULTS: Magnetic resonance angiography revealed an anomalous OA, lateral to the carotid artery and emanating from a branch of the middle meningeal artery. CONCLUSION: OA anomalies should be added to the differential diagnosis of risk factors for unilateral progressive glaucomatous optic neuropathy, and neuroradiologic imaging should be considered to detect such anatomic variants.

Longitudinal CSF isoprostane and MRI atrophy in the progression to AD.

Very little data exist to evaluate the value of longitudinal CSF biological markers for Alzheimer's disease (AD). Most studies indicate that tau and amyloid beta markers do not reflect disease progression. We now report on a longitudinal, three-time point, CSF Isoprostane (IsoP) and quantitative MRI study that examined 11 normal elderly (NL) volunteers and 6 Mild Cognitive Impairment (MCI) patients. After 4 years, all 6 MCI patients declined to AD and 2 of the NL subjects declined to MCI. At baseline and longitudinally, the MCI patients showed reduced delayed memory, increased IsoP levels, and reduced medial temporal lobe gray matter concentrations as compared to NL. A group comprised of all decliners to AD or to MCI (n = 8) was distinguished at baseline from the stable NL controls (n = 9) by IsoP with 100% accuracy.Moreover, both at baseline and longitudinally, the IsoP measures significantly improved the diagnostic and predictive outcomes of conventional memory testing and quantitative MRI measurements. These data indicate that IsoP is potentially useful for both the early detection of AD-related pathology and for monitoring the course of AD.

Imaging and CSF studies in the preclinical diagnosis of Alzheimer's disease.

It is widely believed that the path to early and effective treatment for Alzheimer's disease (AD) requires the development of early diagnostic markers that are both sensitive and specific. To this aim, using longitudinal study designs, we and others have examined magnetic resonance imaging (MRI), 2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG/PET), and cerebrospinal fluid (CSF) biomarkers in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI). Such investigations have led to the often replicated findings that structural evidence of hippocampal atrophy as determined by MRI, as well as metabolic evidence from FDG-PET scan of hippocampal damage, predicts the conversion from MCI to AD. In this article we present a growing body of evidence of even earlier diagnosis. Brain pathology can be detected in NL subjects and used to predict future transition to MCI. This prediction is enabled by examinations revealing reduced glucose metabolism in the hippocampal formation (hippocampus and entorhinal cortex [EC]) as well as by the rate of medial temporal lobe atrophy as determined by MRI. However, neither regional atrophy nor glucose metabolism reductions are specific for AD. These measures provide secondary not primary evidence for AD. Consequently, we will also summarize recent efforts to improve the diagnostic specificity by combining imaging with CSF biomarkers and most recently by evaluating amyloid imaging using PET. We conclude that the combined use of conventional imaging, that is MRI or FDG-PET, with selected CSF biomarkers incrementally contributes to the early and specific diagnosis of AD. Moreover, selected combinations of imaging and CSF biomarkers measures are of importance in monitoring the course of AD and thus relevant to evaluating clinical trials.

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment.

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment.

Cross-sectional cerebrospinal fluid (CSF) levels of tau and amyloid (A) beta (beta) are of diagnostic importance for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, most longitudinal studies of tau fail to demonstrate progression. Because predominantly brain-derived proteins such as tau, have higher ventricle to lumbar ratios, we hypothesized that adjusting for the ventricular enlargement of AD would correct for the dilution of tau, and improve detection of longitudinal change. Abeta which is not exclusively brain derived, shows a ratio <1, and no benefit was expected from adjustment. In a 1 year longitudinal study of eight MCI and ten controls, we examined CSF levels of hyperphosphorylated (P) tau231, Abeta40, and Abeta42. In cross-section, MCI patients showed elevated Ptau231 and Abeta40 levels, and greater ventricular volumes. Longitudinally, only after adjusting for the ventricular volume and only for Ptau231, were increases seen in MCI. Further studies are warranted on mechanisms of tau clearance and on using imaging to interpret CSF studies.

Volumetric analysis of the pre-frontal regions: findings in aging and schizophrenia.

Frontal lobe dysfunction is thought to be involved in schizophrenia and age-associated cognitive decline. Frontal lobe volume changes have been investigated in these conditions using MRI, but results have been inconsistent. Few volumetric MRI protocols exist that divide the pre-frontal cortex into its sub-regions. In the present article, we describe a new method, which allows assessment of the superior, middle and inferior frontal gyrus, as well as the orbitofrontal and cingulate regions. The method uses multiple planes to help guide the anatomical decisions and combines this with a geometric approach utilizing readily apparent anatomical landmarks. Using this protocol, the frontal lobe volumes in young healthy subjects were contrasted with those of young schizophrenic patients and elderly healthy subjects (nine male subjects per group). The results showed that the method could be reproduced with high reliability (r(icc)> or =0.88-0.99). Schizophrenic as well as old subjects had specific significant reductions in the superior frontal gyrus and orbitofrontal regions compared with the young group. However, old and schizophrenic subjects did not differ from each another. No volume differences were observed in the other three regions assessed. Whether or not these volume reductions reflect a common pathological process remains to be investigated in future studies.

Lumbar spinal stenosis assessment with computed tomography, magnetic resonance imaging, and myelography.

Degenerative spinal stenosis of the lumbar spine is caused by many factors, some of which include: disc herniation, ligamentum flavum and facet hypertrophy, spondylolisthesis, and compression fracture. Most often the stenosis is caused by a combination of these factors. The imaging modalities in routine use to evaluate these conditions are computed tomography, magnetic resonance imaging and computed tomography-myelogram. They each have their advantages and disadvantages although any one of these modalities can adequately diagnose lumbar stenosis. The overall accuracy rate of computed tomography, magnetic resonance imaging, and computed tomography-myelogram has been reported to be similar and even complimentary. It is recommended that the least invasive modality be performed first. Magnetic resonance imaging should be the first choice because it does not require ionizing radiation or contrast injection. The aim of the current study is to present the common causes of lumbar stenosis. Where appropriate, each case is shown with images from each modality so that their similarities and differences can be highlighted.

The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease.

For 11 AD cases and four normal elderly controls, post mortem volumes of the hippocampal subdivisions were calculated by using magnetic resonance imaging and histological sections. After at least six weeks of fixation in formalin, brains were examined on a 1.5-T Philips Gyroscan imager producing T1-weighted coronal images with a 3-mm slice thickness. Brains were then processed and embedded in paraffin. Serial coronal sections, 3 mm apart and stained with Cresyl Violet, were used for the planimetry and unbiased estimation of the total numbers of neurons in the hippocampal subdivisions. For all 15 cases, magnetic resonance imaging- and histology-based measurements were performed along the whole rostrocaudal extent of the hippocampal formation and included three subvolumes: (i) the hippocampus (CA1-CA4 and the dentate gyrus); (ii) hippocampus/subiculum; and (iii) hippocampus/parahippocampal gyrus. After controlling for shrinkage, strong correlations were found between magnetic resonance imaging and histological measurements for the hippocampus (r = 0.97, P < 0.001), hippocampus/subiculum (r = 0.95, P < 0.001) and hippocampus/parahippocampal gyrus (r = 0.89, P < 0.001). We also calculated the total number of neurons in the hippocampus and hippocampus/subiculum subvolumes. Strong correlations between the magnetic resonance imaging subvolumes and neuronal counts were found for the hippocampus (r = 0.90, P < 0.001) and the hippocampus/subiculum subvolume (r = 0.84, P < 0.001). We conclude that very accurate volumetric measurements of the whole hippocampal formation can be obtained by using a magnetic resonance imaging protocol. Moreover, the strong correlations between magnetic resonance imaging-based hippocampal volumes and neuronal numbers suggest the anatomical validity of magnetic resonance imaging volume measurements.

Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease.

There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimer's disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory.

Optimizing radiologic costs in the DRG environment.

Previously developed consensus algorithms expressing a suggested radiologic workup for the diagnostic related groups (DRGs) specified by the prospective reimbursement policy have proven to be useful tools for investigating radiologic decision making and the resulting economic implications. The mathematical equations for determining diagnostic and therapeutic costs for two alternative algorithms for suspected acute cholecystitis are formulated. Illustrative examples and graphic displays are given regarding how such algorithms and equations are useful in finding answers to questions about the appropriate diagnostic workup, time, and cost. Exploration of the effect of different parameter values on the choice of the appropriate algorithm is illustrated.

Bilateral cholesterol granulomas of the petrous apices: case report and review.

This paper describes the diagnostic investigations and surgical treatment of a patient with bilateral lesions of the petrous apices. Many surgical methods were considered before choosing one that would allow simultaneous drainage and hearing preservation. A transsphenoidal, transclival route was used and the surgical goals achieved. A review of the pertinent otologic, neurosurgical and radiologic literature is presented. To our knowledge, this is the first case report in the English language of the transclival approach to both petrous apices.

Mascara and eyelining tattoos: MRI artifacts.

Magnetic resonance imaging (MRI) is very useful in the evaluation of ocular and orbital disease. Heavy metal particles, used in the pigment base of mascara and eyelining tattoos, have a paramagnetic effect that causes alteration of the local magnetic field in adjacent tissues. These changes in normal signal result in distortion of the globes. In some cases, the distortion may mimic actual ocular disease such as a ciliary body melanoma or cyst.

Computed tomography versus magnetic resonance imaging of the brain. A collaborative interinstitutional study.

A retrospective study (1983-1984) of magnetic resonance imaging (MRI) and computed tomography (CT) examinations in 471 patients with known pathology in the brain and craniocervical junction was conducted in order to determine the relative efficacy of MRI versus CT. All MRI examinations involved slice thickness greater than 10 mm, and only single-slice single-echo or multislice single-echo imaging techniques were available. These studies were evaluated independently by two neuroradiologists from a panel of six for anatomic abnormalities, lesion contrast, and radiologist's impression. Results, which excluded microadenomas of the pituitary and approximately 9% of studies in which consensus was not achieved by the readers, were as follows: (1) 14% of the studies were positive on MRI but normal on CT; (2) in 55% of the studies, MRI was better than CT; (3) MRI was equal or better than CT in 95% of the studies; and (4) CT was better than MRI in 5% (21/421) of the examinations. There were no patients in this series where CT was positive but MRI missed the abnormality.

Advanced diagnostic imaging techniques in ophthalmology.

Diagnostic imaging techniques continue to gain tremendous importance in the evaluation of ocular and orbital disease as technical developments and refinements are made. This article presents key diagnostic imaging methods, with special focus directed toward the advanced modalities important in evaluation of the traumatized eye and orbit. The text has been prepared specifically for the clinical ophthalmologist. Each of the diagnostic modalities discussed is presented in terms of its basic biophysical mechanism, indications, and advantages and disadvantages. The techniques described include simple plain film roentgenography (and its contrast-related applications: dacryocystography, orbital venography, and angiography), axial hypocycloidal tomography, computed tomography, ultrasonography, and magnetic resonance imaging.

Periventricular hyperintensity as seen by magnetic resonance: prevalence and significance.

Periventricular hyperintensity was identified using long repetition and echo times in spin-echo magnetic resonance imaging of patients with white-matter disease (e.g., multiple sclerosis) caused by local demyelination and in hydrocephalic patients caused by transependymal migration of spinal fluid. A review of 365 consecutives studies revealed that some degree of periventricular hyperintensity is present in most patients (93.5%) regardless of diagnosis. Mild periventricular hyperintensity was seen in patients with no other evidence of intracranial pathology. Periventricular hyperintensity is a normal finding that should not be considered indicative of either demyelinating disease or hydrocephalus. More extensive and severe periventricular hyperintensity is associated with intracerebral pathology, but the finding often is nonspecific. For example, mild periventricular edema from hydrocephalus is impossible to differentiate from the increased periventricular hyperintensity seen in patients with multiple white-matter lesions. Thus, the pattern of periventricular hyperintensity has proven to be of limited value in the clinical assessment of hydrocephalic patients.