Longitudinal trajectories of Alzheimer's disease CSF biomarkers and blood pressure in cognitively healthy subjects.

Introduction: We examined whether hypertension (HTN) was associated with Alzheimer's disease-related biomarkers in cerebrospinal fluid (CSF) and how changes in blood pressure (BP) related to changes in CSF biomarkers over time.

Methods: A longitudinal observation of cognitively healthy normotensive subjects (n = 134, BP < 140/90, with no antihypertensive medication), controlled HTN (n = 36, BP < 140/90, taking antihypertensive medication), and 35 subjects with uncontrolled HTN (BP ≥ 140/90). The follow-up range was 0.

Quantifying cerebrospinal fluid dynamics: A review of human neuroimaging contributions to CSF physiology and neurodegenerative disease.

Cerebrospinal fluid (CSF), predominantly produced in the ventricles and circulating throughout the brain and spinal cord, is a key protective mechanism of the central nervous system (CNS). Physical cushioning, nutrient delivery, metabolic waste, including protein clearance, are key functions of the CSF in humans. CSF volume and flow dynamics regulate intracranial pressure and are fundamental to diagnosing disorders including normal pressure hydrocephalus, intracranial hypotension, CSF leaks, and possibly Alzheimer's disease (AD).

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.

The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease.

Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade.

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance.

Greater specificity for cerebrospinal fluid P-tau231 over P-tau181 in the differentiation of healthy controls from Alzheimer's disease.

Cerebrospinal fluid (CSF) measures of phosphorylated-tau (P-tau) 231 and P-tau181 are two biomarkers for the identification of tau pathology as related to Alzheimer's disease (AD). While both are pathologically validated, their relative diagnostic performances are not well known. This cross-sectional diagnostic study of 87 normal (NL) subjects and 28 AD subjects compared CSF P-tau231 with CSF P-tau181.

Acute diplopia as the presenting sign of silent sinus syndrome.

Silent sinus syndrome is a rare acquired condition that typically presents as enophthalmos and hypoglobus due to atelectasis of the maxillary sinus. The chronic negative pressure in the sinus slowly retracts the orbital floor, altering orbital anatomy and affecting the function of orbital contents. The authors present the first case of acute vertical diplopia as the presenting symptom of silent sinus syndrome.

Plasma BDNF levels vary in relation to body weight in females.

Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects.

Reversible hyperglycemic homonymous hemianopia.

We report a 67-year-old female diabetic with homonymous hemianopia as the presenting sign of nonketotic hyperglycemia. Magnetic resonance imaging (MRI) was abnormal with diffuse bilateral hyperintense white matter changes. A follow-up MRI scan 15 years later showed persisting abnormality.

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.

Lateral rectus muscle palsy, facial numbness and ataxia as the initial manifestation of multiple sclerosis.

Lateral rectus muscle (LRM) palsy due to a nuclear or fascicular sixth nerve lesion is rare as the presenting sign of multiple sclerosis (MS). It is more common to find this palsy in the company of other nearby cranial nerves deficits. Facial numbness in association with a LRM palsy or paresis may go unappreciated and therefore underreported.

An entorhinal cortex sulcal pattern is associated with Alzheimer's disease.

Objectives: Magnetic resonance (MRI) studies rely on sulcal boundaries to delineate the human entorhinal cortex (EC) and typically show that EC size is reduced in Alzheimer's disease (AD) and a predictor of future dementia. However, it is unknown if variations in the EC sulcal patterns are associated with AD. We classified the lateral EC sulcal boundary as either a rhinal or collateral pattern and tested the hypotheses that the rhinal pattern was (1) more common in AD and (2) associated with a smaller EC size.

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.

The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease.

While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60+/-10 years, range 36-86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Abeta42/Abeta40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by epsilon4 genotype interactions were found for P-tau231 (beta=1.

Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment.

Objectives: To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD).

Methods: A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau(231)), amyloid beta (Abeta) Abeta(42)/Abeta(40) ratio, isoprostane (IP) as well as P-tau(231)/Abeta(42/40) and T-tau/Abeta(42/40) ratios.

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.

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.

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.

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.

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.

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.

Postoperative gas bubble foot drop. A case report.

Study Design: An unusual case of foot drop occurring 10 days after disc surgery is reported. Imaging studies identified a gas bubble compressing the nerve root.

Objective: To describe the origin and management of a radiculopathy caused by an intraspinal gas bubble.